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Research Paper|Volume 13, Issue 14|pp 18223—18237

Combination of rapamycin and SAHA enhanced radiosensitization by inducing autophagy and acetylation in NSCLC

Yong Wang1, Fen Liu2, Chen Fang1, Liyao Xu3, Lin Chen4, Zeyao Xu2, Jiaquan Chen2, Wei Peng2, Biqi Fu5, Yong Li1
  • 1Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China
  • 2Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China
  • 3Department of Paediatrics, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
  • 4Department of Internal Neurology, Jiangxi Provincial People's Hospital, Nanchang 330000, China
  • 5Department of Rheumatology, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China
Received: February 22, 2021Accepted: May 31, 2021Published: July 28, 2021
https://doi.org/10.18632/aging.203226

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.