Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway

He, Yang; Cao, Lingling; Wang, Li; Liu, Lingping; Huang, Ying; Gong, Xuan

The previous study has shown that LRP2 is mainly involved in regulations on lipoprotein transporter activity, low-density lipoprotein receptor activity, lipid metabolic process, lipoprotein transport, coronary vasculature development, aorta development, cell proliferation, ventricular septum development, clathrin-coated vesicle membrane, lysosome, etc. It is of significance in the etiology of acute myocardial infarction. 17, 18 The JNK pathway is extensively involved in cellular behaviors, and its dysregulation is considered to be linked to disease progression. [19] [20] [21] In MGC-803 cells (gastric cancer cells), JNK induces apoptosis through the mitochondrial pathway, triggering cytochrome release into the cytoplasm to initiate the apoptotic pathway. 21, 22 Besides, metformin is able to activate the AMPK, mTOR/6SK, p-ERK and p70S6K/pS6 pathways. 14, 23 It is capable of suppressing mitosis and proliferation of thyroid cancer stem cells and induces apoptosis. 24 Our findings illustrated that metformin treatment inactivated the JNK pathway in TPC-1 cells, which could be abolished by overexpression of LRP2.