title: Overexpression of the BRIP1 ameliorates chemosensitivity to cisplatin by inhibiting Rac1 GTPase activity in cervical carcinoma HeLa cells.
abstract: BRCA1-interacting protein 1 (BRIP1), a DNA-dependent ATPase and a DNA helicase, is critical for BRCA-associated DNA damage repair functions and may be associated with the tumourigenesis and aggressiveness of various cancers. Here, we constructed a BRIP1 recombinant plasmid, overexpressed it in a cervical cancer cell line (HeLa) and found that ectopic expression of BRIP1 could remarkably enhance the antitumor activity of cisplatin, as demonstrated by decreased cell viability, colony formation and tumour xenografts' weight. Moreover, BRIP1 promoted cisplatin-mediated cell apoptosis and suppressed tumour angiogenesis. We also found that the synergistic inhibition effect of BRIP1 might be partially attributed to attenuation of Rac1 GTPase activation and that Rac1 GTPase re-activation could reverse the sensitizing effect induced by BRIP1. Our study suggested that up-regulation of BRIP1 could enhance chemosensitivity of HeLa cells to cisplatin through inhibiting Rac1 GTPase activation, and it provides a new insight into the essential role of BRIP1 in cervical cancer chemotherapy.
authors.affiliation: Department of Combination of Traditional Chinese and Western Medicine, Shaanxi Provincial Tumor Hospital, Xi'an 710061, Shaanxi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gynaecology and Obstetrics, Xi'an XD Group Hospital, Xi'an 710077, Shaanxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Methadone Maintenance Treatment Clinic, Xi'an Mental Health Center, Xi'an 710061, Shaanxi, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China. Electronic address: danghuimin1968@163.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Dang
authors.affiliation: Department of Gynaecology and Oncology, Shaanxi Provincial Tumor Hospital, Xi'an 710065, Shaanxi, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Gynaecology and Oncology, Shaanxi Provincial Tumor Hospital, Xi'an 710065, Shaanxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi'an 710065, Shaanxi, China.
authors.forename: Yongtong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi'an 710065, Shaanxi, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Combination of Traditional Chinese and Western Medicine, Shaanxi Provincial Tumor Hospital, Xi'an 710061, Shaanxi, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C107953:RAC1 protein, human; C000618935:BRIP1 protein, human; D020365:RNA Helicases; D020830:rac1 GTP-Binding Protein; D002945:Cisplatin
keywords: BRIP1; Cervical cancer; Chemosensitivity; Cisplatin