Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (5): 876-886.DOI: 10.19852/j.cnki.jtcm.20230802.004
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Active compounds of Caodoukou (Semen Alpinia Katsumadai) inhibit the migration, invasion and metastasis of human pancreatic cancer cells by targeting phosphoinosmde-3-kinase/ protein kinase B/mammalian target of rapamycin pathway
YANG Xiaohui1, WANG Jian1, CHENG Li1, ZHANG Yuxi1, HUANG Jianlin2,3(
), LIU Minghua1()
- 1 Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
2 Department of Pharmacy, Luzhou Naxi District People's Hospital, Luzhou 646000, China
3 Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
-
Received:2022-09-16Accepted:2022-12-19Online:2023-10-15Published:2023-08-02 -
Contact:HUANG Jianlin, Department of Pharmacy, Luzhou Naxi District People's Hospital, Luzhou 646000, China.375088566@qq.com ;Prof. LIU Minghua, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.99053808@qq.com . Telephone: +86-15082083009 -
Supported by:Sichuan Science and Technology program: Study on the Molecular Mechanism and Reversal Strategy of Drug Resistance in “T + A” Therapy for Liver Cancer(2022YSF0625);Joint Project from Luzhou city and Southwest Medical University: Study on Preparation and Anti-colon Cancer Activity of PEG-PLGA Nanoparticles from Active Fraction of Clove(20ykdhz0008);Grants from National Natural Science Foundation of China: Study on the Interaction between Granulin A and ENO1 and Its Molecular Mechanism of Inhibiting Tumor Growth and Metastasis(81773776)
Cite this article
YANG Xiaohui, WANG Jian, CHENG Li, ZHANG Yuxi, HUANG Jianlin, LIU Minghua. Active compounds of Caodoukou (Semen Alpinia Katsumadai) inhibit the migration, invasion and metastasis of human pancreatic cancer cells by targeting phosphoinosmde-3-kinase/ protein kinase B/mammalian target of rapamycin pathway[J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 876-886.
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Figure 1 Active compounds of Alpinia katsumadai (ACAK) inhibited migration and invasion of human PANC-1 and PANC-28 cells A: PANC-1 cells were treated with various concentrations of ACAK (10, 20 and 40 μg/mL), and the migration of PANC-1 cells was determined by Scratch wound healing assay. B: results of quantitative analysis of PANC-1 scratch assays. C: PANC-28 cells were treated with various concentrations of ACAK (10, 20 and 40 μg/mL), and the migration of PANC-28 cells was determined by Scratch wound healing assay. D: results of quantitative analysis of PANC-28 scratch assay. Figure E, F, G and H using crystal violet staining. PANC-1 and PANC-28 cells were treated with various concentrations of ACAK (10, 20 and 40 μg/mL). Transwell assay was also performed to determine the migration and invasion of PANC-1 cells (E, G) and PANC-28 cells (F, H) treated with ACAK. The data are representative of at least three independent experiments (n > 3) in triplicate and are expressed as mean ± standard deviation. aP < 0.05 and bP < 0.01 vs control by One-way ANOVA followed by Tukey’s multiple comparison test. E1, F1, G1, H1 and control: only treated with RPMI-1640/DMEM; E2, F2, G2, H2 and DMSO: treated with RPMI-1640/DMEM and DMSO; E3, F3, G3, H3 and 10 μg/mL: treated with RPMI-1640/DMEM, DMSO and 10 μg/mL ACAK; E4, F4, G4, H4 and 20 μg/mL: treated with RPMI-1640/DMEM, DMSO and 20 μg/mL ACAK; E5, F5, G5, H5 and 40 μg/mL: treated with RPMI-1640/DMEM, DMSO and 40 μg/mL ACAK. DMEM: dulbecco's modified eagle medium; DMSO: dimethyl sulfoxide; PANC-1/28: pancreatic cancer cell 1/28; ANOVA: analysis of variance; RPMI: roswell memorial institute; ACAK: active compounds of Caodoukou (Semen Alpinia Katsumadai).
Figure 1 Active compounds of Alpinia katsumadai (ACAK) inhibited migration and invasion of human PANC-1 and PANC-28 cells A: PANC-1 cells were treated with various concentrations of ACAK (10, 20 and 40 μg/mL), and the migration of PANC-1 cells was determined by Scratch wound healing assay. B: results of quantitative analysis of PANC-1 scratch assays. C: PANC-28 cells were treated with various concentrations of ACAK (10, 20 and 40 μg/mL), and the migration of PANC-28 cells was determined by Scratch wound healing assay. D: results of quantitative analysis of PANC-28 scratch assay. Figure E, F, G and H using crystal violet staining. PANC-1 and PANC-28 cells were treated with various concentrations of ACAK (10, 20 and 40 μg/mL). Transwell assay was also performed to determine the migration and invasion of PANC-1 cells (E, G) and PANC-28 cells (F, H) treated with ACAK. The data are representative of at least three independent experiments (n > 3) in triplicate and are expressed as mean ± standard deviation. aP < 0.05 and bP < 0.01 vs control by One-way ANOVA followed by Tukey’s multiple comparison test. E1, F1, G1, H1 and control: only treated with RPMI-1640/DMEM; E2, F2, G2, H2 and DMSO: treated with RPMI-1640/DMEM and DMSO; E3, F3, G3, H3 and 10 μg/mL: treated with RPMI-1640/DMEM, DMSO and 10 μg/mL ACAK; E4, F4, G4, H4 and 20 μg/mL: treated with RPMI-1640/DMEM, DMSO and 20 μg/mL ACAK; E5, F5, G5, H5 and 40 μg/mL: treated with RPMI-1640/DMEM, DMSO and 40 μg/mL ACAK. DMEM: dulbecco's modified eagle medium; DMSO: dimethyl sulfoxide; PANC-1/28: pancreatic cancer cell 1/28; ANOVA: analysis of variance; RPMI: roswell memorial institute; ACAK: active compounds of Caodoukou (Semen Alpinia Katsumadai).
Figure 2 ACAK inhibited mRNA expression of PANC-1 and PANC-28 metastasis-related molecules PANC-1 and PANC-28 cells were treated with various concentrations of ACAK (5, 10 and 20 μg/mL). A-D: effect of ACAK on mRNA expression of molecules related to migration invasion of PANC-1 cells. A: MMP-2; B: MMP-9; C: E-cadherin; D: N-cadherin. E-H: effect of ACAK on mRNA expression of molecules related to migration invasion in PANC-28 cells. E: MMP-2; F: MMP-9; G: E-cadherin; H: N-cadherin. Control: only treated with RPMI-1640/DMEM; DMSO: treated with RPMI-1640/DMEM and DMSO; 10 μg/mL: treated with RPMI-1640/DMEM, DMSO and 10 μg/mL ACAK; 20 μg/mL: treated with RPMI-1640/DMEM, DMSO and 20 μg/mL ACAK; 40 μg/mL: treated with RPMI-1640/DMEM, DMSO and 40 μg/mL ACAK. DMEM: dulbecco's modified eagle medium; DMSO: dimethyl sulfoxide. PANC-1/28: pancreatic cancer cell 1/28; RPMI: roswell memorial institute; ACAK: active compounds of Caodoukou (Semen Alpinia Katsumadai). The inhibitory effect of ACAK on the expression of mRNA related to migration and invasion of pancreatic cancer cells was dose-dependent. Experiments were repeated 3 times and expressed as mean ± standard deviation (n = 3). aP < 0.01, bP < 0.001, cP < 0.05, compared with control group by one-way analysis of variance followed by Tukey’s multiple comparison test.
Figure 2 ACAK inhibited mRNA expression of PANC-1 and PANC-28 metastasis-related molecules PANC-1 and PANC-28 cells were treated with various concentrations of ACAK (5, 10 and 20 μg/mL). A-D: effect of ACAK on mRNA expression of molecules related to migration invasion of PANC-1 cells. A: MMP-2; B: MMP-9; C: E-cadherin; D: N-cadherin. E-H: effect of ACAK on mRNA expression of molecules related to migration invasion in PANC-28 cells. E: MMP-2; F: MMP-9; G: E-cadherin; H: N-cadherin. Control: only treated with RPMI-1640/DMEM; DMSO: treated with RPMI-1640/DMEM and DMSO; 10 μg/mL: treated with RPMI-1640/DMEM, DMSO and 10 μg/mL ACAK; 20 μg/mL: treated with RPMI-1640/DMEM, DMSO and 20 μg/mL ACAK; 40 μg/mL: treated with RPMI-1640/DMEM, DMSO and 40 μg/mL ACAK. DMEM: dulbecco's modified eagle medium; DMSO: dimethyl sulfoxide. PANC-1/28: pancreatic cancer cell 1/28; RPMI: roswell memorial institute; ACAK: active compounds of Caodoukou (Semen Alpinia Katsumadai). The inhibitory effect of ACAK on the expression of mRNA related to migration and invasion of pancreatic cancer cells was dose-dependent. Experiments were repeated 3 times and expressed as mean ± standard deviation (n = 3). aP < 0.01, bP < 0.001, cP < 0.05, compared with control group by one-way analysis of variance followed by Tukey’s multiple comparison test.
Figure 3 ACAK inhibited migration and invasion of pancreatic cancer cells (PANC-1 and PANC-28 cells) and the activation of the PI3K/Akt/mTOR pathway in PANC-1 and PANC-28 cells A: ACAK inhibits the expression of migratory invasion-associated proteins in PANC-1 cells in a dose-dependent manner; B: ACAK inhibits the expression of migratory invasion-associated proteins in PANC-28 cells in a dose-dependent manner; C: ACAK inhibits the expression of PI3K/Akt/mTOR signaling pathway-related proteins in pancreatic cancer cells in a dose-dependent manner. PI3K: phosphoinosmde-3-kinase; Akt: protein kinase B; mTOR: mammalian target of rapamycin; MMP-2/-9: matrix metallopeptidase 2/9. Experiments were repeated 3 times.
Figure 3 ACAK inhibited migration and invasion of pancreatic cancer cells (PANC-1 and PANC-28 cells) and the activation of the PI3K/Akt/mTOR pathway in PANC-1 and PANC-28 cells A: ACAK inhibits the expression of migratory invasion-associated proteins in PANC-1 cells in a dose-dependent manner; B: ACAK inhibits the expression of migratory invasion-associated proteins in PANC-28 cells in a dose-dependent manner; C: ACAK inhibits the expression of PI3K/Akt/mTOR signaling pathway-related proteins in pancreatic cancer cells in a dose-dependent manner. PI3K: phosphoinosmde-3-kinase; Akt: protein kinase B; mTOR: mammalian target of rapamycin; MMP-2/-9: matrix metallopeptidase 2/9. Experiments were repeated 3 times.
Table 2 ACAK inhibited the tumor growth in xenograft nude mice model
| Group | n | Volumes (mm3) | Tumor inhibition rate (%) | |
|---|---|---|---|---|
| Before administration | After administration | |||
| Negative control | 6 | 116±15 | 654±204 | - |
| Solvent control | 6 | 113±16 | 652±216 | - |
| Positive control (TGO) | 6 | 120±15 | 283±62 | 56.86 |
| Low dosage (50 mg/kg) | 6 | 113±15 | 539±145 | 17.65 |
| Medium dosage (100 mg/kg) | 6 | 114±17 | 352±105 | 46.21 |
| High dosage (200 mg/kg) | 6 | 116±21 | 318±68 | 51.36 |
Table 2 ACAK inhibited the tumor growth in xenograft nude mice model
| Group | n | Volumes (mm3) | Tumor inhibition rate (%) | |
|---|---|---|---|---|
| Before administration | After administration | |||
| Negative control | 6 | 116±15 | 654±204 | - |
| Solvent control | 6 | 113±16 | 652±216 | - |
| Positive control (TGO) | 6 | 120±15 | 283±62 | 56.86 |
| Low dosage (50 mg/kg) | 6 | 113±15 | 539±145 | 17.65 |
| Medium dosage (100 mg/kg) | 6 | 114±17 | 352±105 | 46.21 |
| High dosage (200 mg/kg) | 6 | 116±21 | 318±68 | 51.36 |
Figure 4 ACAK inhibited the tumor growth of PANC-1 xenograft being in nude mice A: ACAK inhibited the tumor growth in xenograft nude mice model; B: tumor volume of each nude mice group; C: the effect of ACAK on the weight of nude mice; D: effect of ACAK on lung metastasis of xenograft tumor in nude mice (hematoxylin-eosin staining, ×200). D1: Normal lung tissue; D2: Negative control; D3: Positive control; D4: ACAK 50 mg/kg; D5: ACAK 100 mg/kg; D6: ACAK 200 mg/kg. Negative control: treated only with normal saline; solvent control: treated with normal saline and Carboxymethylcellulose Sodium Lubricant; positive control: treated with normal saline, Carboxymethylcellulose Sodium Lubricant and TGO; low dosage (50 mg/kg): treated with normal saline, carboxymethylcellulose sodium lubricant, TGO and 50 mg/kg ACAK; medium dosage (100 mg/kg): treated with normal saline, Carboxymethylcellulose Sodium Lubricant, TGO and 100 mg/kg ACAK; high dosage (200 mg/kg): treated with normal saline, carboxymethylcellulose sodium lubricant, TGO and 200 mg/Kg ACAK; TGO: tegafur gimeracil oteracil potassium. The data are expressed as mean ± standard deviation (n = 6).
Figure 4 ACAK inhibited the tumor growth of PANC-1 xenograft being in nude mice A: ACAK inhibited the tumor growth in xenograft nude mice model; B: tumor volume of each nude mice group; C: the effect of ACAK on the weight of nude mice; D: effect of ACAK on lung metastasis of xenograft tumor in nude mice (hematoxylin-eosin staining, ×200). D1: Normal lung tissue; D2: Negative control; D3: Positive control; D4: ACAK 50 mg/kg; D5: ACAK 100 mg/kg; D6: ACAK 200 mg/kg. Negative control: treated only with normal saline; solvent control: treated with normal saline and Carboxymethylcellulose Sodium Lubricant; positive control: treated with normal saline, Carboxymethylcellulose Sodium Lubricant and TGO; low dosage (50 mg/kg): treated with normal saline, carboxymethylcellulose sodium lubricant, TGO and 50 mg/kg ACAK; medium dosage (100 mg/kg): treated with normal saline, Carboxymethylcellulose Sodium Lubricant, TGO and 100 mg/kg ACAK; high dosage (200 mg/kg): treated with normal saline, carboxymethylcellulose sodium lubricant, TGO and 200 mg/Kg ACAK; TGO: tegafur gimeracil oteracil potassium. The data are expressed as mean ± standard deviation (n = 6).
| 1. |
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-87.
DOI PMID |
| 2. | Liu X, Li T, Huang X, et al. DEPDC1B promotes migration and invasion in pancreatic ductal adenocarcinoma by activating the Akt/GSK3β/Snail pathway. Oncol Lett 2020; 20: 1. |
| 3. |
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30.
DOI URL |
| 4. |
Cavallaro U, Christofori G. Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann NY Acad Sci 2004; 1014: 58-66.
PMID |
| 5. |
Cao X, He Q. Anti-tumor activities of bioactive phytochemicals in Sophora flavescens for breast cancer. Cancer Manag Res 2020; 12: 1457-67.
DOI URL |
| 6. |
Qi F, Zhao L, Zhou A, et al. The advantages of using Traditional Chinese Medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends 2015; 9: 16-34.
DOI PMID |
| 7. |
Lee SE, Shin HT, Hwang HJ, Kim JH. Antioxidant activity of extracts from Alpinia katsumadai seed. Phytother Res 2003; 17: 1041-7.
PMID |
| 8. |
Li H, Park JH, Lee JC, et al. Neuroprotective effects of Alpinia katsumadai against experimental ischemic damage via control of oxidative stress. Pharm Biol 2013; 51: 197-205.
DOI URL |
| 9. |
Tan Y, Zheng C. Effects of Alpinetin on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium-induced ulcerative colitis mice. Am J Med Sci 2018; 355: 377-86.
DOI PMID |
| 10. | Liu Y, Wang K, Feng Q, et al. Alpinetin attenuates persistent inflammation, immune suppression, and catabolism syndrome in a septic mouse model. J Immunol Res 2021; 2021: 9998517. |
| 11. | Wang CC, Lu JW, Peng YJ, et al. Ameliorative effects of Cardamonin on monosodium urate-induced gouty arthritis through inhibiting NLRP 3 inflammasome iediation. Medicina (Kaunas, Lithuania) 2021; 57. |
| 12. | Wang XQ, Yang XJ, Li JS. Studies on chemical constituents of alpinia katsumadai. Zhong Yao Cai 2008; 31: 853-5. |
| 13. |
Klančnik A, Gröblacher B, Kovač J, Bucar F, Možina SS. Anti-Campylobacter and resistance-modifying activity of Alpinia katsumadai seed extracts. J Appl Microbiol 2012; 113: 1249-62.
DOI PMID |
| 14. |
Zhang T, Guo S, Zhu X, Qiu J, Deng G, Qiu C. Alpinetin inhibits breast cancer growth by ROS/NF-κB/HIF-1α axis. J Cell Mol Med 2020; 24: 8430-40.
DOI PMID |
| 15. |
Cheng Y, Dai C, Zhang J. SIRT3-SOD2-ROS pathway is involved in linalool-induced glioma cell apoptotic death. Acta Biochim Pol 2017; 64: 343-50.
DOI PMID |
| 16. |
Kim YJ, Kang KS, Choi KC, Ko H. Cardamonin induces autophagy and an antiproliferative effect through JNK activation in human colorectal carcinoma HCT116 cells. Bioorg Med Chem Lett 2015; 25: 2559-64.
DOI URL |
| 17. |
Lim W, Park S, Bazer FW, Song G. Naringenin-induced apoptotic cell death in prostate cancer cells is mediated via the PI3K/AKT and MAPK signaling pathways. J Cell Biochem 2017; 118: 1118-31.
DOI URL |
| 18. |
Wang HX, Tang C. Galangin suppresses human laryngeal carcinoma via modulation of caspase-3 and AKT signaling pathways. Oncol Rep 2017; 38: 703-14.
DOI URL |
| 19. |
Chaffer CL, San Juan BP, Lim E, Weinberg RA. EMT, cell plasticity and metastasis. Cancer Metastasis Rev 2016; 35: 645-54.
DOI URL |
| 20. |
Chen T, You Y, Jiang H, Wang ZZ. Epithelial-mesenchymal transition (EMT): a biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol 2017; 232: 3261-72.
DOI PMID |
| 21. |
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-74.
DOI PMID |
| 22. | Noronha C, Ribeiro AS, Taipa R, et al. Cadherin expression and EMT: a focus on gliomas. Biomedicines 2021; 9. |
| 23. |
Zhang X, Liu G, Kang Y, Dong Z, Qian Q, Ma X. N-cadherin expression is associated with acquisition of EMT phenotype and with enhanced invasion in erlotinib-resistant lung cancer cell lines. PLoS One 2013; 8: e57692.
DOI URL |
| 24. |
Jia H, Zhang Q, Liu F, Zhou D. Prognostic value of MMP-2 for patients with ovarian epithelial carcinoma: a systematic review and Meta-analysis. Arch Gynecol Obstet 2017; 295: 689-96.
DOI PMID |
| 25. |
Liu G, Jiang C, Li D, Wang R, Wang W. MiRNA-34a inhibits EGFR-signaling-dependent MMP7 activation in gastric cancer. Tumour Biol 2014; 35: 9801-6.
DOI URL |
| 26. | Zhang GJ, Zhao J, Jiang ML, Zhang LC. ING5 inhibits cell proliferation and invasion in esophageal squamous cell carcinoma through regulation of the Akt/NF-κB/MMP-9 signaling pathway. Biochem Biophys Resh Commun 2018; 496: 387-93. |
| 27. |
Fattahi S, Amjadi-Moheb F, Tabaripour R, Ashrafi GH, Akhavan-Niaki H. PI3K/AKT/mTOR signaling in gastric cancer: epigenetics and beyond. Life Sci 2020; 262: 118513.
DOI URL |
| 28. | Jin Y, Feng SJ, Qiu S, Shao N, Zheng JH. LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway. Eur Rev Med Pharmacol Sci 2017; 21: 3176-84. |
| 29. |
Zhang L, Liang H, Xin Y. Cucurbitacin E inhibits esophageal carcinoma cell proliferation, migration, and invasion by suppressing Rac1 expression through PI3K/AKT/mTOR pathway. Anticancer Drugs 2020; 31: 847-55.
DOI PMID |
| 30. |
Song L, Zhang H, Hu M, et al. Sinomenine inhibits hypoxia induced breast cancer side population cells metastasis by PI3K/Akt/mTOR pathway. Bioorg Med Chem 2021; 31: 115986.
DOI URL |
| 31. |
Yang N, Hui L, Wang Y, Yang H, Jiang X. SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway. Oncol Rep 2014; 31: 2651-9.
DOI URL |
| 32. | Liu M, Zhao G, Zhang D, et al. Active fraction of clove induces apoptosis via PI3K/Akt/mTOR-mediated autophagy in human colorectal cancer HCT-116 cells. Int J Oncol 2018; 53: 1363-73. |
| 33. |
Li C, Xu H, Chen X, et al. Aqueous extract of clove inhibits tumor growth by inducing autophagy through AMPK/ULK pathway. Phytother Res 2019; 33: 1794-804.
DOI PMID |
| 34. |
Wu N, Zhang C, Wang C, et al. Zinc-doped copper oxide nanocomposites reverse temozolomide resistance in glioblastoma by inhibiting AKT and ERK1/2. Nanomedicine (London, England) 2018; 13: 1303-18.
DOI URL |
| 35. |
Xu B, Guo M, Ma L, et al. Mere15, a novel polypeptide from Meretrix meretrix, inhibits proliferation and metastasis of human non-small cell lung cancer cells through regulating the PI3K/Akt/mTOR signaling pathway. Neoplasma 2021; 68: 1181-89.
DOI PMID |
| 36. |
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109-10.
DOI PMID |
| 37. |
Polivka JR, Janku F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther 2014; 142: 164-75.
DOI URL |
| 38. |
Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 2014; 4: 64.
DOI PMID |
| 39. |
Hong C, Lishan W, Peng X, et al. Hsa_circ_0074298 promotes pancreatic cancer progression and resistance to gemcitabine by sponging miR-519 to target SMOC. J Cancer 2022; 13: 34-50.
DOI PMID |
| 40. |
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19: 1423-37.
DOI PMID |
| 41. |
Tang B, Du J, Wang J, et al. Alpinetin suppresses proliferation of human hepatoma cells by the activation of MKK7 and elevates sensitization to cis-diammined dichloridoplatium. Oncol Rep 2012; 27: 1090-6.
DOI PMID |
| 42. |
Shrivastava S, Jeengar M, Thummuri D, et al. Cardamonin, a chalcone, inhibits human triple negative breast cancer cell invasiveness by downregulation of Wnt/β-catenin signaling cascades and reversal of epithelial-mesenchymal transition. BioFactors (Oxford, England) 2017; 43: 152-69.
DOI URL |
| 43. |
Niu PG, Zhang YX, Shi DH, Liu Y, Chen YY, Deng J. Cardamonin inhibits metastasis of Lewis lung carcinoma cells by decreasing mTOR activity. PLoS One 2015; 10: e0127778.
DOI URL |
| 44. |
Gobin E, Bagwell K, Wagner J, et al. A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential. BMC Cancer 2019; 19: 581.
DOI PMID |
| 45. | Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 Biosensors: recent advances. Sensors (Basel) 2018; 18. |
| 46. |
Kesh K, Subramanian L, Ghosh N, et al. A/G promoter polymorphism with gastric cancer risk: Influence of nicotine in differential allele-specific transcription via increased phosphorylation of CREB. J Biol Chem 2015; 290: 14391-406.
DOI URL |
| 47. |
Ichimaru Y, Sano M, Kajiwara I, et al. Indirubin 3'-Oxime inhibits migration, invasion, and metastasis in vivo in mice bearing spontaneously occurring pancreatic cancer via blocking the RAF/ERK, AKT, and SAPK/JNK pathways. Transl Oncol 2019; 12: 1574-82.
DOI PMID |
| 48. |
Yang H, Dai G, Wang S, et al. Inhibition of the proliferation, migration, and invasion of human breast cancer cells by leucine aminopeptidase 3 inhibitors derived from natural marine products. Anticancer Drugs 2020; 31: 60-6.
DOI PMID |
| 49. |
Zhou P, Li XP, Jiang R, et al. Evodiamine inhibits migration and invasion by Sirt1-mediated post-translational modulations in colorectal cancer. Anticancer Drugs 2019; 30: 611-7.
DOI PMID |
| 50. |
Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012; 366: 109-19.
DOI URL |
| 51. |
Celia-Terrassa T, Meca-Cortes O, Mateo F, et al. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Invest 2012; 122: 1849-68.
DOI URL |
| 52. |
Chaw SY, Abdul Majeed A, Dalley AJ, Chan A, Stein S, Farah CS. Epithelial to mesenchymal transition (EMT) biomarkers--E-cadherin, beta-catenin, APC and Vimentin--in oral squamous cell carcinogenesis and transformation. Oral Oncol 2012; 48: 997-1006.
DOI PMID |
| 53. |
Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7: 131-42.
DOI |
| 54. | Zhang X, Liu G, Kang Y, Dong Z, Qian Q, Ma X. N-cadherin expression is associated with acquisition of EMT phenotype and with enhanced invasion in erlotinib-resistant lung cancer cell lines. PLoS One 2013; 8. |
| 55. |
Brouxhon SM, Kyrkanides S, Teng X, et al. Soluble E-cadherin: a critical oncogene modulating receptor tyrosine kinases, MAPK and PI3K/Akt/mTOR signaling. Oncogene 2014; 33: 225-35.
DOI PMID |
| 56. |
Sarbassov DD, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159-68.
DOI PMID |
| 57. | Ma Z, Lou S, Jiang Z. PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway. Aging (Albany NY) 2020; 12: 7985-8000. |
| 58. |
Wei R, Xiao Y, Song Y, Yuan H, Luo J, Xu W. FAT4 regulates the EMT and autophagy in colorectal cancer cells in part via the PI3K-AKT signaling axis. J Exp Clin Cancer Res 2019; 38: 112.
DOI |
| 59. |
Xu W, Yu M, Qin J, Luo Y, Zhong M. LACTB regulates PIK3R3 to promote autophagy and inhibit EMT and proliferation through the PI3K/AKT/mTOR signaling pathway in colorectal cancer. Cancer Manag Res 2020; 12: 5181-200.
DOI PMID |
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