Suppresses of LIM kinase 2 promotes radiosensitivity in radioresistant non-small cell lung cancer cells

Chao Tian; Zhen Peng; Lei Chang; Xinzhou Deng; Shan Jiang; Jiahui Han; Can Ye; Yutao Yan; Zhiguo Luo

doi:10.1016/j.heliyon.2023.e22090

Suppresses of LIM kinase 2 promotes radiosensitivity in radioresistant non-small cell lung cancer cells

Heliyon. 2023 Nov 8;9(11):e22090. doi: 10.1016/j.heliyon.2023.e22090. eCollection 2023 Nov.

Authors

Chao Tian¹, Zhen Peng¹, Lei Chang², Xinzhou Deng¹, Shan Jiang¹, Jiahui Han³, Can Ye¹, Yutao Yan¹, Zhiguo Luo¹

Affiliations

¹ Department of Clinical Oncology, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
² Department of Urology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
³ Department of Clinical Oncology, Taihe Hospital, Jinzhou Medical University Union Training Base, Shiyan, Hubei, 442000, China.

Abstract

Radiation resistance has always been one of the main obstacles to tumor radiotherapy. Therefore, understanding the mechanisms underlying radiotherapy resistance is a focus of research. In this study, we induced two radiation-resistant cell lines to mimic the radiation resistance of NSCLC and investigated the mechanisms of radiotherapy resistance. Cell radiosensitivity was analyzed by single-cell gel electrophoresis, colony formation and tumor sphere formation assays. A wound healing assay was used to analyze cell migration. Western blotting and siRNA were used to identify the potential mechanism. In animal model experiments, xenograft tumors were used to verify the difference between radiotherapy-resistant and nonresistant NSCLC models after radiotherapy. Our results showed that NSCLC radiation-resistant cells exhibited more radioresistance and migratory abilities under low-dose irradiation. The expression of LIMK2 and p-CFL1 were upregulated in NSCLC radiation-resistant cells. Knockdown of LIMK2 significantly enhanced the radiosensitivity of NSCLC-resistant cells. In vivo, low-dose radiotherapy suppressed tumor growth, induced apoptosis and upregulated the expression of LIMK2 in xenograft tumors. However, radiotherapy had little effect on the NSCLC radiation resistance model. In conclusion, NSCLC radiation-resistant cells exhibit more radioresistance and migratory ability under low-dose irradiation. Strikingly, knockdown of LIMK2 enhanced the radiosensitivity of NSCLC-resistant cells.

Keywords: Clone formation; LIMK2; Migration; NSCLC; Radiation resistance.