1. Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
2. Department of General Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China
3. Department of Mechanical Engineering, Johns Hopkins University, Baltimore 21218, USA
4. Department of Respiration, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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.
Keywords: Klotho, cellular senescence, lung cancer, IL-6