Abstract：Objective: To explore the effects of bortezomib on apoptosis and invasion of human thyroid carcinoma (TC) cells and its possible mechanism. Methods: Human papillary thyroid carcinoma B-CPAP cells were cultured in vitro, and the experimental concentration and time of bortezomib were screened with MTT; thyroid carcinoma B-CPAP cells at the exponential growth stage were divided into control group, AICAR group (AMPK activator 2 mmol/L), bortezomib (50nmol/L) group, bortezomib + Compound C group (bortezomib 50nmol/L + AMPK inhibitor Compound C 5μmol/L); flow cytometry to detect the apoptosis rate of B-CPAP cells in each group; Transwell test to detect cell invasion ability; Western Blot to detect apoptosis, invasion and the expression of AMPK/mTOR/4EBP1 pathway-related proteins [B-cell lymphoma/leukemia-2 gene (Bcl-2), cysteine aspartic protease-3 (Caspases-3), E-cadherin, β-catenin, adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and its phosphorylated protein].Results: Different concentrations of bortezomib inhibited the growth of B-CPAP cells to varying degrees. Compared with the control group, the apoptosis rate of B-CPAP cells, the expression of Caspases-3, E-cadherin, β-catenin, and the ratio of p-AMPK/AMPK were significantly higher in the AICAR and bortezomib groups (P<0.05), and the entry Transwell lower layer, expression of Bcl-2, p-mTOR/mTOR, and p-4EBP1/4EBP1 ratio were significantly lower (P<0.05), and there was no statistically significant difference between the AICAR and bortezomib groups (P>0.05); the use of AMPK inhibitor Compound C elevated the ratios of p-mTOR/mTOR, p-4EBP1/4EBP1, and significantly reduced the inhibitory effect and the pro-apoptotic effect of bortezomib on the invasion of thyroid carcinoma B-CPAP cells.Conclusion: Bortezomib inhibits the proliferation and invasion of human thyroid carcinoma cells, and induce apoptosis. Its mechanism may be related to the activation of AMPK and inhibition of mTOR and 4EBP1 activation.
贺椿媛, 梁金环, 王翠, 徐倩. 硼替佐米对人甲状腺癌细胞凋亡侵袭及AMPK/mTOR/4EBP1通路的影响[J]. 河北医学, 2022, 28(4): 544-549.
HE Chunyuan, LIANG Jinhuan, WANG Cui, et al. Effects of Bortezomib on Apoptosis Invasion and AMPK/mTOR/4EBP1 Pathway in Human Thyroid Carcinoma Cells. HeBei Med, 2022, 28(4): 544-549.
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2022, Vol. 28 
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