Chen Bo, Liang Yan, Chen Liben, Wei Yunyan, Li Yue, Zhao Weihong, Wu Jianqing
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Department of General Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
J Cancer. 2018 Mar 14;9(7):1248-1258. doi: 10.7150/jca.23967. eCollection 2018.
Lung cancer (LC) is the most common cause of death from cancer worldwide, and it is also a closely aging-related disease. Klotho, a new anti-aging gene, has been proven to play a critical role in regulating aging and the development of age-related diseases including LC. However, whether Klotho is a key link between aging and LC is still unknown. Here we report that Klotho can indirectly inhibit LC growth and development through regulating senescence-associated secretory phenotype (SASP). We found that senescent lung fibroblasts (SLF) can promote production of IL-6 and IL-8, which can be effectively inhibited by overexpressing Klotho. Using conditioned medium (CM) derived from SLF to culture LC cells, the LC cells show obvious increase of viability and migration rates, significant increase expression of p-STAT3 and α-SMA, and decrease expression of P53 and E-cadherin. However, using CM derived from SLF overexpressed Klotho to culture LC cells, all above results are nearly completely reversed. Thus, these results suggest that Klotho can regulate SLF extracellular release of IL-6 and IL-8, which can influence STAT3 activation, P53 expression and epithelial-mesenchymal transition (EMT) of LC cells, finally inhibiting LC cells growth and migration indirectly.
肺癌（LC）是全球癌症死亡的最常见原因，也是一种与衰老密切相关的疾病。Klotho作为一种新的抗衰老基因，已被证明在调节衰老以及包括肺癌在内的与年龄相关疾病的发展中起着关键作用。然而，Klotho是否是衰老与肺癌之间的关键联系仍不清楚。在此我们报告，Klotho可通过调节衰老相关分泌表型（SASP）间接抑制肺癌的生长和发展。我们发现衰老的肺成纤维细胞（SLF）可促进IL-6和IL-8的产生，而过表达Klotho可有效抑制这种产生。用来自SLF的条件培养基（CM）培养肺癌细胞，肺癌细胞的活力和迁移率明显增加，p-STAT3和α-SMA的表达显著增加，而P53和E-钙黏蛋白的表达降低。然而，用来自过表达Klotho的SLF的CM培养肺癌细胞，上述所有结果几乎完全逆转。因此，这些结果表明，Klotho可调节SLF细胞外IL-6和IL-8的释放，这可影响肺癌细胞的STAT3激活、P53表达和上皮-间质转化（EMT），最终间接抑制肺癌细胞的生长和迁移。
