SIRT6 through PI3K/Akt/mTOR signaling pathway to enhance radiosensitivity of non-Small cell lung cancer and inhibit tumor progression.

Abstract

To explore the effect and mechanism of SIRT6 on radiosensitivity and tumor progression of non-small cell lung cancer (NSCLC). qRT-PCR was performed to detect the expressions of SIRT6 in tumor tissues, adjacent normal tissues and NSCLC cell lines of patients with advanced NSCLC before and after radiotherapy. After overexpression or interference with SIRT6 expression in NSCLC cells, the cells were routinely cultured or transfected for 48 h followed by 4Gy radiation for 24 h. Then, check the cell proliferation, migration, apoptosis and cell cycle by MTT, wound healing assay and flow cytometry, while detect the expression of PI3K/Akt/mTOR signaling pathway-related proteins by Western blot. In addition, the effect of SIRT6 expression on NSCLC tumor growth was analyzed by xenograft tumor assay. SIRT6 showed a low expression in NSCLC tumor tissues and cell lines, while SIRT6 was significantly increased in NSCLC tissues after radiation treatment. Overexpression of SIRT6 in A549 and NCI-H23 cells inhibited cell proliferation viability, migration ability and promoted apoptosis. By comparison, after radiation treatment, NSCLC cells with high SIRT6 expression had lower ability of proliferation and migration and higher apoptosis rate. Overexpression of SIRT6 evidently down-regulated the activity of PI3K/Akt/mTOR signaling pathway in NSCLC cells before and after radiation. In addition, H2009 cells exhibited opposite cellular functions after interference with SIRT6 expression. In vivo experiments showed that overexpression of SIRT6 promoted the inhibitory effect of radiation on the growth of NSCLC xenograft tumors in nude mice. SIRT6 can promote the radiosensitivity of NSCLC and inhibit the development of tumor by down-regulating the activity of PI3K/Akt/mTOR signaling pathway.