title: ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response.
abstract: ARRB1 (also known as β-arrestin-1) 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.
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Liguang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Tiehong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Cao
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000071559:beta-Arrestin 1 / Q000378:metabolism*
chemical_list: C000605253:ARRB1 protein, human; D000970:Antineoplastic Agents; D000071559:beta-Arrestin 1; D002945:Cisplatin