自噬
辐射敏感性
癌症研究
乙酰化
DNA损伤
组蛋白脱乙酰基酶
放射治疗
DNA修复
A549电池
化学
组蛋白
细胞凋亡
生物
医学
DNA
生物化学
内科学
基因
作者
Yong Wang,Fen Liu,Fang Chen,Liyao Xu,Lin Chen,Zeyao Xu,Jiaquan Chen,Wei Peng,Biqi Fu,Yong Li
出处
期刊:Aging
[Impact Journals, LLC]
日期:2021-07-28
卷期号:13 (14): 18223-18237
被引量:6
标识
DOI:10.18632/aging.203226
摘要
Radiotherapy plays an essential role in the treatment of non-small-cell lung cancer (NSCLC). However, cancer cells' resistance to ionizing radiation (IR) is the primary reason for radiotherapy failure leading to tumor relapse and metastasis. DNA double-strand breaks (DSB) repair after IR is the primary mechanism of radiotherapy resistance. In this study, we investigated the effects of autophagy-inducing agent, Rapamycin (RAPA), combined with the histone deacetylase inhibitor (HDACi), Suberoylanilide Hydroxamic Acid (SAHA), on the radiosensitivity of A549 and SK-MES-1 cells, and examined the combination effects on DNA damage repair, and determined the level of autophagy and acetylation in A549 cells. We also investigated the combination treatment effect on the growth of A549 xenografts after radiotherapy, and the level of DNA damage, autophagy, and acetylation. Our results showed that RAPA combined with SAHA significantly increased the inhibitory effect of radiotherapy compared with the single treatment group. The combined treatment increased the expression of DNA damage protein γ-H2AX and decreased DNA damage repair protein expression. RAPA combined with SAHA was induced mainly by regulating acetylation levels and autophagy. The effect of combined treatment to increase radiotherapy sensitivity will be weakened by inhibiting the level of autophagy. Besides, the combined treatment also showed a significantly inhibited tumor growth in the A549 xenograft model. In conclusion, these results identify a potential therapeutic strategy of RAPA combined with SAHA as a radiosensitizer to decreased DSB repair and enhanced DNA damage by inducing acetylation levels and autophagy for NSCLC.
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