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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
Received date: 2022-09-16
Accepted date: 2022-12-19
Online published: 2023-08-02
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)
OBJECTIVE: To detect the effects of active compounds of Caodoukou (Semen Alpinia Katsumadai) (ACAK) on the proliferation, migration and invasion of pancreatic cancer, and explain the possible molecular mechanism of ACAK interacting with these processes.
METHODS: Cell counting kit-8 method, cell scratch repair experiment, Transwell migration and invasion experiment, immunohistochemistry, western blot assay and real-time polymerase chain reaction experiment were used to evaluate the effect of ACAK on the proliferation, migration and invasion of pancreatic cancer cells. The levels of active molecules involved in the phosphoinosmde-3-kinase (PI3K)/Akt/the mammalian target of rapamycin (mTOR) signal transduction were detected by Western blot assay. In addition, the function of ACAK in vivo was evaluated by xenotransplantation tumor model in nude mice.
RESULTS: The inhibitory effect of ACAK on the proliferation of pancreatic cancer cells showed certain time-dose dependence. The results of scratch repair test, Transwell test, Western blotting and real time polymerase chain reaction assay showed that ACAK could inhibit the migration and invasion of pancreatic cancer cells in vitro. In addition, the regulatory effect of ACAK on epithelial-mesenchymal transition (EMT) is partly attributed to PI3K/Akt/mTOR signaling pathway. The experimental results in vivo showed that ACAK regulated the development of pancreatic cancer.
CONCLUSIONS: ACAK can partly inhibit the activity of EMT and matrix metallopeptidases by down-regulating the downstream proteins of PI3K/Akt/mTOR signal pathway, thus inhibiting the ability of migration and invasion of pancreatic cancer.
Xiaohui YANG , Jian WANG , Li CHENG , Yuxi ZHANG , Jianlin HUANG , Minghua LIU . 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 . DOI: 10.19852/j.cnki.jtcm.20230802.004
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