ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response
作者
Shen, HC;Wang, LG;Zhang, JG;Dong, W;Zhang, TH;Ni, Y;Cao, HX;Wang, K;Li, Y;Wang, YB;Du, JJ
作者单位
[Shen, Hongchang; Wang, Liguang; Zhang, Tiehong; Ni, Yang] Shandong Univ, Shandong Prov Hosp, Dept Oncol, Jinan 250021, Shandong, Peoples R China.;-;[Wang, Liguang; Zhang, Jiangang; Cao, Hongxin; Wang, Kai; Du, Jiajun] Shandong Univ, Shandong Prov Hosp, Inst Oncol, Jinan 250021, Shandong, Peoples R China.;-;[Dong, Wei; Li, Yun; Du, Jiajun] Shandong Univ, Shandong Prov Hosp, Dept Thorac Surg, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.;-;[Wang, Yibing] Shandong Univ, Shandong Prov Hosp, Dept Surg, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.
摘要
ARRB1 (also known as beta-arresting) serves as a multifunctional adaptor contributing to the regulation of signaling pathways. ARRB1 may be involved in DNA damage accumulation; however the underlying mechanism involved is unclear. In the present study, non-small cell lung cancer (NSCLC) cell lines (H520 and SK-MES-1) were transfected with ARRB1 plasmids or small interfering ribonucleic acid (siRNA) and received treatment with DNA-damaging agents (cisplatin and etoposide). A mouse xenograft model was used to assess the impact of ARRB1 on the efficacy of cisplatin in vivo. A total of 30 surgically resected NSCLC patients were recruited for the present study and qRT-PCR was performed to determine the mRNA levels in cancer tissues compared with para-carcinoma tissues. Our data showed that DNA damage was abrogated in the ARRB1-knockdown cells and enhanced in the ARRB1-overexpressing cells. ATR and Chk1 were more activated in the ARRB1-overexpressing cells compared to the ARRB1-knockdown cells, followed by increased H2AX phosphorylation. DNA damage and apoptosis were increased in the ARRB1-overexpressing cells treated with cisplatin. These data provided strong evidence that ARRB1 contributes to the response of NSCLC to DNA-damaging agents and is essential for DNA damage response (DDR). ARRB1 may enhance the efficacy of DNA-damaging agents in NSCLC.
关键词
FLOW-CYTOMETRY; BETA-ARRESTINS; CELL; CARCINOMA; APOPTOSIS; BETA-ARRESTIN-1; EXPRESSION; PROGNOSIS; THERAPY; ASSAY
基本信息
