Journal of Traditional Chinese Medicine >
Dujieqing decoction (毒结清复方) suppresses multiple myeloma growth by inhibiting the Wnt/β-catenin pathway
Received date: 2024-06-12
Accepted date: 2024-11-18
Online published: 2025-07-25
Supported by
National Science Foundation-Funded Project: based on the Connection Sclerostin with Wnt/β-catenin Pathway to Explored the Effect Mechanism of Dujieqing Oral Liquid on the Inhibit Tumor and Promote Bone Formation in Multiple Myeloma(81960839);Innovation Project of Guangxi Graduate Education-Funded Project: Sclerostin Regulates Wnt/β-catenin Pathway to Explore the Mechanism of Dujieqing Decoction in Inhibiting Tumor Growth and Promoting Osteogenesis of Multiple Myeloma(YCSW2021224);To Investigate the Effect and Mechanism of Dujiangqing Oral Liquid on Osteogenic Differentiation of Mesenchymal Stem Cells in Multiple Myeloma Mice based on Wnt/β-catenin Signaling Pathway(YCSW2023386)
OBJECTIVE: To explore the therapeutic potential of the Dujieqing (DJQ) decoction (毒结清复方) for multiple myeloma (MM) and elucidate its mechanism of action.
METHODS: RPMI8226 cells were treated with DJQ-containing serum (DJQ-CS) and a Wnt/β-catenin pathway inhibitor, XAV-939. Cell counting kit-8 assay was used to examine cell viability, and flow cytometry was performed to examine apoptosis. Real-time polymerase chain reaction and Western blotting were used to evaluate the Wnt/β-catenin pathway family members in the cells. Subsequently, the RPMI8226 cells were subcutaneously injected into the left flank of none obesity disease and server combined immune-deficiency mice to replicate the xenograft tumor mouse models, which were treated with the DJQ decoction for 14 d. Hematoxylin and eosin staining was used to examine the pathological changes of the liver and kidney tissues, and to detect xenograft tumors. Wnt/β-catenin pathway family members were evaluated via Western blotting.
RESULTS: DJQ-CS significantly reduced the mRNA and protein expression levels of β-catenin, c-myc, cyclin D1, and lymphoid enhancer binding factor 1 (LEF1) while inhibiting the proliferation of RPMI8226 cells and inducing their apoptosis. Similar results were observed when the Wnt/β-catenin pathway was suppressed by inhibitors. Moreover, in the mouse model of xenograft tumors, DJQ decoction not only reduced the tumor volume but also inhibited the protein levels of β-catenin, c-myc, cyclin D1, and LEF1. The histopathology of the mice also showed increased apoptosis in tumor tissues, while the DJQ decoction treatment did not cause any pathological damage to the kidneys or liver.
CONCLUSION: Our results indicate that the DJQ decoction suppresses tumor progression by inhibiting the Wnt/β-catenin pathway, offering a promising treatment approach for MM.
Key words: multiple myeloma; Wnt signaling pathway; beta Catenin; Dujieqing decoction
Jiawei XU , Haisong LU , Yushi SHI , Yu LEI , Xueping LI , Weimin CHENG . Dujieqing decoction (毒结清复方) suppresses multiple myeloma growth by inhibiting the Wnt/β-catenin pathway[J]. Journal of Traditional Chinese Medicine, 2025 , 45(4) : 720 -729 . DOI: 10.19852/j.cnki.jtcm.2025.04.002
| 1. | Huang J, Chan SC, Lok V, et al. The epidemiological landscape of multiple myeloma: a global cancer registry estimate of disease burden, risk factors, and temporal trends. Lancet Haematol 2022; 9: e670-7. |
| 2. | Dima D, Jiang D, Singh DJ, et al. Multiple myeloma therapy: emerging trends and challenges. Cancers (Basel) 2022; 14: 4082. |
| 3. | Luo H, Vong CT, Chen H, et al. Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine. Chin Med 2019; 14: 48. |
| 4. | Fan Y, Ma Z, Zhao L, et al. Anti-tumor activities and mechanisms of Traditional Chinese Medicines formulas: a review. Biomed Pharmacother 2020; 132: 110820. |
| 5. | Dai H, Ma B, Dai X, et al. Shengma biejia decoction inhibits cell growth in multiple myeloma by inducing autophagy-mediated apoptosis through the ERK/mTOR pathway. Front Pharmacol 2021; 12: 585286. |
| 6. | Chen P, Wu S, Dong X, Zhou M, Xu P, Chen B. Formosanin C induces autophagy-mediated apoptosis in multiple myeloma cells through the PI3K/AKT/mTOR signaling pathway. Hematology 2022; 27: 977-86. |
| 7. | Lei Y, Guo YH, Xu JW, et al. To explore the mechanism and experimental verification of Dujieqing decoction (毒结清复方) on multiple myeloma based on network pharmacology. Zhong Yi Yao Dao Bao 2023; 29: 17-23. |
| 8. | Yu S, Han R, Gan R. The Wnt/β-catenin signalling pathway in haematological neoplasms. Biomark Res 2022; 10: 74. |
| 9. | van Andel H, Kocemba KA, Spaargaren M, Pals ST. Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options. Leukemia 2019; 33: 1063-75. |
| 10. | Gao Y, Li L, Hou L, Niu B, Ru X, Zhang D. SOX12 promotes the growth of multiple myeloma cells by enhancing Wnt/β-catenin signaling. Exp Cell Res 2020; 388: 111814. |
| 11. | Chen SY, Zhang GC, Shu QJ. Yangyin Jiedu decoction overcomes gefitinib resistance in non-small cell lung cancer via down-regulation of the PI3K/Akt signalling pathway. Pharm Biol 2021; 59: 1294- 304. |
| 12. | Lyu M, Liu Q. JMJD2C triggers the growth of multiple myeloma cells via activation of β-catenin. Oncol Rep 2021; 45: 1162-70. |
| 13. | Yuan Y, Guo M, Gu C, Yang Y. The role of Wnt/β-catenin signaling pathway in the pathogenesis and treatment of multiple myeloma (review). Am J Transl Res 2021; 13: 9932-49. |
| 14. | Rafae A, van Rhee F, Al Hadidi S. Perspectives on the treatment of multiple myeloma. Oncologist 2024; 29: 200-12. |
| 15. | Bian Y, Wang G, Zhou J, et al. Astragalus Membranaceus (Huangqi) and Rhizoma Curcumae (Ezhu) decoction suppresses colorectal cancer via downregulation of Wnt5/β-Catenin signal. Chin Med. 2022; 17: 11. |
| 16. | Yang Z, Yao Y, Qian C. Study on the effect of Jianpi Yiqi decoction on clinical symptoms, inflammation, oxidative stress, efficacy and adverse reactions in sufferers with colorectal cancer. Biotechnol Genet Eng Rev 2024; 40: 3019-34. |
| 17. | Xin XL, Wang GD, Han R, et al. Mechanism underlying the effect of Liujunzi decoction on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy. J Tradit Chin Med 2022; 42: 108-15. |
| 18. | Gong H, Chen W, Mi L, et al. Qici Sanling decoction suppresses bladder cancer growth by inhibiting the Wnt/Β-catenin pathway. Pharm Biol 2019; 57: 507-13. |
| 19. | Cheng Z, Ye F, Xu C, et al. The potential mechanism of Longsheyangquan decoction on the treatment of bladder cancer: Systemic network pharmacology and molecular docking. Front Pharmacol 2022; 13: 932039. |
| 20. | Yu CC, Li Y, Cheng ZJ, Wang X, Mao W, Zhang YW. Active components of traditional Chinese medicinal material for multiple myeloma: current evidence and future directions. Front Pharmacol 2022; 13: 818179. |
| 21. | Zheng J, Chen Y, Zheng Z, et al. In vitro investigation of the cytotoxic activity of emodin 35 derivative on multiple myeloma cell lines. Evid Based Complement Alternat Med 2021; 2021: 6682787. |
| 22. | Gu C, Yin Z, Nie H, et al. Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1. BMC Biol 2020; 18: 33. |
| 23. | Hashemzaei M, Delarami Far A, Yari A, et al. Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo. Oncol Rep 2017; 38: 819-28. |
| 24. | Sougiannis AT, VanderVeen B, Chatzistamou I, et al. Emodin reduces tumor burden by diminishing M2-like macrophages in colorectal cancer. Am J Physiol Gastrointest Liver Physiol 2022; 322: G383-95. |
| 25. | Dai G, Wang D, Ma S, et al. ACSL 4 promotes colorectal cancer and is a potential therapeutic target of emodin. Phytomedicine 2022; 102: 154149. |
| 26. | Salama AAA, Allam RM. Promising targets of chrysin and daidzein in colorectal cancer: amphiregulin, CXCL1, and MMP-9. Eur J Pharmacol 2021; 892: 173763. |
| 27. | Liu Y, Luo X, Liu J, et al. Shenlingcao oral liquid for patients with non-small cell lung cancer receiving adjuvant chemotherapy after radical resection: a multicenter randomized controlled trial. Phytomedicine 2023; 113: 154723. |
| 28. | Cichocki F, Zhang B, Wu CY, et al. Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma. Sci Transl Med 2023; 15: eade3341. |
| 29. | Tabana YM, Hassan LE, Ahamed MB, et al. Scopoletin, an active principle of tree tobacco (Nicotiana glauca) inhibits human tumor vascularization in xenograft models and modulates ERK1, VEGF-A, and FGF-2 in computer model. Microvasc Res 2016; 107: 17-33. |
| 30. | Mu Q, Najafi M. Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells. Int Immunopharmacol 2021; 98: 107895. |
| 31. | Wang H, Yu D, Zhang H, et al. Quercetin inhibits the proliferation of multiple myeloma cells by upregulating PTPRR expression. Acta Biochim Biophys Sin (Shanghai) 2021; 53: 1505-15. |
| 32. | Xu YW, Zou LF, Li F. Effect of Quercetin on proliferation and apoptosis of multiple myeloma cells and its related mechanism. Zhong Guo Shi Yan Xue Ye Xue Za Zhi 2020; 28: 1234-9. |
| 33. | Hsu CM, Yen CH, Wang SC, et al. Emodin ameliorates the efficacy of carfilzomib in multiple myeloma cells via apoptosis and autophagy. Biomedicines 2022; 10: 1638. |
| 34. | Ma R, Yu D, Peng Y, et al. Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells. Acta Biochim Biophys Sin (Shanghai) 2021; 53: 775-83. |
| 35. | Geng W, Guo X, Zhang L, et al. Resveratrol inhibits proliferation, migration and invasion of multiple myeloma cells via NEAT1-mediated Wnt/β-catenin signaling pathway. Biomed Pharmacother 2018; 107: 484-94. |
| 36. | Zhang C, Hao Y, Sun Y, Liu P. Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis. J Pharmacol Sci 2019; 140: 128-36. |
| 37. | Ma W, Liu F, Yuan L, Zhao C, Chen C. Emodin and AZT synergistically inhibit the proliferation and induce the apoptosis of leukemia K562 cells through the EGR1 and the Wnt/β-catenin pathway. Oncol Rep 2020; 43: 260-9. |
| 38. | Razak S, Afsar T, Ullah A, et al. Taxifolin, a natural flavonoid interacts with cell cycle regulators causes cell cycle arrest and causes tumor regression by activating Wnt/β-catenin signaling pathway. BMC Cancer 2018; 18: 1043. |
| 39. | Sun WD, Zhu XJ, Li JJ, Mei YZ, Li WS, Li JH. Nicotinamide N-methyltransferase (NNMT): a key enzyme in cancer metabolism and therapeutic target. Int Immunopharmacol 2024; 142: 113208. |
| 40. | Sakthivel KM, Vishnupriya S, Priya Dharshini LC, Rasmi RR, Ramesh B. Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of Scopoletin. J Pharm Pharmacol 2022; 74: 147-61. |
| 41. | Cilibrasi C, Riva G, Romano G, et al. Resveratrol impairs glioma stem cells proliferation and motility by modulating the Wnt signaling pathway. PLoS One 2017; 12: e0169854. |
| 42. | Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol 2020; 13: 165. |
| 43. | S?derholm S, Cantù C. The WNT/β-catenin dependent transcription: a tissue-specific business. WIREs Mech Dis 2021; 13: e1511. |
| 44. | Zheng L, Zheng Q, Yu Z, et al. Liuwei Dihuang pill suppresses metastasis by regulating the wnt pathway and disrupting-catenin/T cell factor interactions in a murine model of triple-negative breast cancer. J Tradit Chin Med 2019; 39: 826-32. |
| 45. | Wu Y, Fang G, Wang X, et al. NUP 153 overexpression suppresses the proliferation of colorectal cancer by negatively regulating Wnt/β-catenin signaling pathway and predicts good prognosis. Cancer Biomark 2019; 24: 61-70. |
| 46. | Tang Y, Song G, Liu H, Yang S, Yu X, Shi L. Silencing of long non-coding RNA HOTAIR alleviates epithelial-mesenchymal transition in pancreatic cancer via the Wnt/β-catenin signaling pathway. Cancer Manag Res 2021; 13: 3247-57. |
| 47. | Liu X, Zuo X, Sun X, Tian X, Teng Y. Hexokinase 2 promotes cell proliferation and tumor formation through the Wnt/β-catenin pathway-mediated cyclin D1/c-myc upregulation in epithelial ovarian cancer. J Cancer 2022; 13: 2559-69. |
| 48. | Pandit H, Li Y, Li X, Zhang W, Li S, Martin RCG. Enrichment of cancer stem cells via β-catenin contributing to the tumorigenesis of hepatocellular carcinoma. BMC Cancer 2018; 18: 783. |
| 49. | Liu X, Huang Y, Zhang Y, et al. T-cell factor (TCF/LEF1) binding elements (TBEs) of FasL (Fas ligand or CD95 ligand) bind and cluster Fas (CD95) and form complexes with the TCF-4 and b-catenin transcription factors in vitro and in vivo which result in triggering cell death and/or cell activation. Cell Mol Neurobiol 2016; 36: 1001-13. |
| 50. | Li C, Zheng X, Han Y, Lyu Y, Lan F, Zhao J. XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Oncol Lett 2018; 15: 8973-82. |
| 51. | Pan F, Shen F, Yang L, Zhang L, Guo W, Tian J. Inhibitory effects of XAV939 on the proliferation of small-cell lung cancer H446 cells and Wnt/β-catenin signaling pathway in vitro. Oncol Lett 2018; 16: 1953-8. |
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