title: Silencing of CXCR4 sensitizes triple-negative breast cancer cells to cisplatin.
abstract: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer for which there is no effective treatment. Previously, we and others demonstrated that CXCR4 surface expression is an independent prognostic factor for disease relapse and survival in breast cancer. In this study, we investigated the effects of CXCR4 gene silencing on cisplatin chemosensitivity in human triple-negative breast cancer cell lines. We found that CXCR4 silencing significantly inhibited cell growth, decreased colony formation, and enhanced cisplatin sensitivity while overexpression of CXCR4 rendered cells more resistant to cisplatin. Moreover, the percentage of apoptosis and cell cycle arrest at the G2/M phase of cisplatin-treated CXCR4 knockdown cells was significantly higher than control cells. Furthermore, we demonstrated CXCR4 knockdown cells showed lower levels of mutant p53 and Bcl-2 protein than the control group, while also having higher levels of caspase-3 and Bax. However overexpression of CXCR4 had the reverse effect. In vivo experiments confirmed that downregulation of CXCR4 enhanced cisplatin anticancer activity in tumor-bearing mice, and that this enhanced anticancer activity is attributable to tumor cell apoptosis. Thus, this study indicates that CXCR4 can modulate cisplatin sensitivity in TNBC cells and suggests that CXCR4 may be a therapeutic target for TNBC.
authors.affiliation: Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Sixian
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Linhao
authors.initials: L
authors.lastname: Xie
authors.affiliation: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Yaochen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Caiwen
authors.initials: C
authors.lastname: Du
authors.affiliation: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D019718:Receptors, CXCR4; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D002945:Cisplatin