自噬
下调和上调
辐射敏感性
细胞凋亡
西妥因1
癌症研究
程序性细胞死亡
细胞生物学
化学
前列腺癌
生物
癌症
放射治疗
医学
内科学
基因
生物化学
遗传学
作者
Kaixuan Wang,Yan Chen,Yang Xu,Pei-Yan Zhu,Wenwen Cui,Cong Ye,Kan Hu,Ting Lan,Linyan Huang,Wan Wang,Ping Ma,Suhua Qi,Bing Gu,Lan Luo
标识
DOI:10.1016/j.bbrc.2022.03.142
摘要
Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC.
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