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 4 Gy 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.

中文翻译：

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SIRT6通过PI3K/Akt/mTOR信号通路增强非小细胞肺癌放射敏感性并抑制肿瘤进展

探讨SIRT6对非小细胞肺癌（NSCLC）放射敏感性及肿瘤进展的影响及机制。采用qRT-PCR检测晚期NSCLC患者放疗前后肿瘤组织、癌旁正常组织和NSCLC细胞系中SIRT6的表达情况。在NSCLC细胞中过表达或干扰SIRT6表达后，将细胞常规培养或转染48小时，然后4 Gy辐射24小时。然后，通过MTT、伤口愈合试验和流式细胞仪检测细胞增殖、迁移、凋亡和细胞周期，同时通过Western blot检测PI3K/Akt/mTOR信号通路相关蛋白的表达。此外，通过异种移植肿瘤试验分析了 SIRT6 表达对 NSCLC 肿瘤生长的影响。SIRT6 在 NSCLC 肿瘤组织和细胞系中呈低表达，而 SIRT6 在放疗后在 NSCLC 组织中显着升高。SIRT6 在 A549 和 NCI-H23 细胞中的过表达抑制细胞增殖活力、迁移能力并促进细胞凋亡。相比之下，放射治疗后，SIRT6高表达的NSCLC细胞增殖和迁移能力较低，凋亡率较高。SIRT6的过表达明显下调了放疗前后NSCLC细胞中PI3K/Akt/mTOR信号通路的活性。此外，H2009 细胞在干扰 SIRT6 表达后表现出相反的细胞功能。体内实验表明，SIRT6的过表达促进了辐射对裸鼠NSCLC异种移植瘤生长的抑制作用。