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Effect Of TAK1 Gene On Proliferation And Metastasis Of Gallbladder Carcinoma Cells

Posted on:2019-12-02Degree:MasterType:Thesis
Country:ChinaCandidate:Z Q LiFull Text:PDF
GTID:2404330569480684Subject:Surgery
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Objective: Because gallbladder cancer(GBC)has many characteristics such as great harm,difficult diagnosis and late treatment,gallbladder cancer is widely regarded as one of the main causes of cancer death worldwide.Transforming growth factor beta activated protein kinase 1(TAK1),or MAP3K7,acts as a member of the mitogen activated protein kinase(MAPKKK)family and participates in the physiological functions of various cells.A large number of research results have shown that TAK1 can act on various tumor cells through some signaling pathways,thereby promoting the proliferation,differentiation,invasion,invasion and metastasis of tumor cells,and causing the occurrence and development of tumors.However,there are few reports about the effect of TAK1 on the occurrence and development of gallbladder cancer.In this study,we explored the effect of TAK1 on gallbladder cancer cells and its mechanism.Methods: In order to understand the expression of TAK1 in gallbladder carcinoma and paracancerous tissues,we performed immunoblotting and RT-PCR test,at the same time,in order to explore the role of TAK1 in the classical PI3K/AKT signaling pathway,we detected the PI3K/AKT signaling pathway related proteins by Western blotting.We also explored the effect of TAK1 on the proliferation of gallbladder cancer cells in vitro by CCK-8 and clone formation experiments.In addition,in order to determine the effect of TAK1 on the migration of gallbladder cancer cells in vitro,we conducted a scratch test and a Transwell lab test.Finally,the mechanism of the action of TAK1 on gallbladder cancer was further verified by establishing a xenotransfer tumor model in nude mice.Results: In this experiment,we found that the expression of TAK1 in all kinds of gallbladder cancer cells was significantly higher than that in the paracancerous tissue,suggesting thatTAK1 may be associated with the occurrence of gallbladder cancer.Then we found that the proliferation and migration of gallbladder cancer cells after knocking down the TAK1 gene were significantly weakened.The model experiment of liver metastases in nude mice showed that TAK1 could promote the metastasis of gallbladder cancer cells in vivo.Conclusion: Through this experiment,we conclude that TAK1 may have a correlation with the classic PI3K/AKT signaling pathway,suggesting that TAK1 promotes the proliferation and metastasis of gallbladder cancer cells through the PI3K/AKT signaling pathway.These findings suggest that TAK1 can be used as a new target molecule for the treatment of gallbladder cancer.
Keywords/Search Tags:Gallbladder cancer, TAK1, Proliferation, Metastasis, PI3K/AKT pathway
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