抗辐射性
赫拉
DNA损伤
癌细胞
细胞凋亡
DNA修复
细胞生物学
细胞周期
生物
辐射敏感性
细胞
癌症研究
DNA
细胞培养
癌症
放射治疗
遗传学
医学
内科学
作者
Jinhua Zhang,Youhua Xie,Xiaoyi Liu,Lu Gan,Pingping Li,Zhihui Dou,Di Chen,Hong Zhang,Jing Si
摘要
Abstract Quiescent cancer cells are major impediments to effective radiotherapy (RT) and exhibit limited sensitivity to traditional photon therapy. Herein, the functional role and underlying mechanism of carbon ions in overcoming the radioresistance of quiescent cervical cancer HeLa cells were determined. Briefly, serum withdrawal was used to induce synchronized quiescence in HeLa cells. Quiescent HeLa cells displayed strong radioresistance and DNA repair potential. After irradiation with carbon ions, the DNA damage repair pathway may markedly rely on error‐prone nonhomologous end‐joining in proliferating cells, whereas the high‐precision homologous recombination pathway is more relevant in quiescent cells. This phenomenon could be explained by the ionizing radiation (IR)‐induced cell cycle re‐entry of quiescent cancer cells. There are three strategies for eradicating quiescent cancer cells using high‐linear energy transfer (LET) carbon ions: direct cell death through complex DNA damage; apoptosis via an enhanced mitochondria‐mediated intrinsic pathway; forced re‐entry of quiescent cancer cells into the cell cycle, thereby improving their susceptibility to IR. Silencing β‐catenin signaling is essential for maintaining the dormant state in quiescent cells. Herein, carbon ions activated the β‐catenin pathway in quiescent cells, and inhibition of this pathway improved the resistance of quiescent HeLa cells to carbon ions by alleviating DNA damage, improving DNA damage repair, maintaining quiescent depth, and inhibiting apoptosis. Collectively, carbon ions conquer the radioresistance of quiescent HeLa cells by activating β‐catenin signaling, which provides a theoretical basis for improved therapeutic effects in patients with middle‐advanced‐stage cervical cancer with radioresistance.
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