二甲双胍通过降低低密度脂蛋白受体相关蛋白2（LRP2）抑制JNK信号通路，从而抑制人甲状腺癌TPC-1细胞的增殖。
Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway.
作者信息
He Yang, Cao Lingling, Wang Li, Liu Lingping, Huang Ying, Gong Xuan
机构信息
Department of Endocrinology, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People's Republic of China.
Department of Endocrinology, Jiujiang No 1 People's Hospital (Affiliated Jiujiang Hospital of Nanchang University), Jiujiang, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Jan 6;13:45-50. doi: 10.2147/OTT.S227915. eCollection 2020.
OBJECTIVE
To uncover the potential effect of metformin on proliferation and apoptosis of thyroid cancer TPC-1 cell line, and the underlying mechanism.
METHODS
Viability, apoptosis and LRP2 level in TPC-1 cells treated with different doses of metformin for different time points were determined. Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot. Regulatory effects of LRP2 on the JNK pathway and cell viability in metformin-treated TPC-1 cells were assessed.
RESULTS
Viability in TPC-1 cells gradually decreased with the treatment of increased doses of metformin either for 24 h or 48 h. The apoptotic rate was concentration-dependently elevated by metformin treatment. Relative levels of LRP2 and p-JNK1 were concentration-dependently downregulated by metformin treatment. In addition, overexpression of LRP2 partially abolished the inhibitory effect of metformin on the viability of TPC-1 cells.
CONCLUSION
Metformin treatment suppresses the proliferative ability and induces apoptosis of TPC-1 cells by downregulating LRP2 to block the JNK pathway.
目的
探讨二甲双胍对甲状腺癌TPC-1细胞系增殖和凋亡的潜在影响及其潜在机制。
方法
测定不同剂量二甲双胍处理不同时间点的TPC-1细胞的活力、凋亡情况及LRP2水平。此外，通过蛋白质免疫印迹法检测二甲双胍处理的TPC-1细胞中p-JNK1和c-Jun氨基末端激酶（JNK）的蛋白质水平。评估LRP2对二甲双胍处理的TPC-1细胞中JNK通路和细胞活力的调节作用。
结果
无论是处理24小时还是48小时，随着二甲双胍剂量增加，TPC-1细胞的活力逐渐降低。二甲双胍处理使凋亡率呈浓度依赖性升高。二甲双胍处理使LRP2和p-JNK1的相对水平呈浓度依赖性下调。此外，LRP2的过表达部分消除了二甲双胍对TPC-1细胞活力的抑制作用。
结论
二甲双胍处理通过下调LRP2以阻断JNK通路，从而抑制TPC-1细胞的增殖能力并诱导其凋亡。
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