451. PCDHGB7 Increases Chemosensitivity to Carboplatin by Inhibiting HSPA9 via Inducing Apoptosis in Breast Cancer.
- Author
-
Hou S, Shan M, Gao C, Feng X, Yang Y, Zhang R, He Y, Zhang G, and Zhang L
- Subjects
- Antineoplastic Agents pharmacology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cadherins genetics, Cell Proliferation drug effects, Female, Humans, Tumor Cells, Cultured, Apoptosis drug effects, Breast Neoplasms drug therapy, Cadherins metabolism, Carboplatin pharmacology, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic drug effects, HSP70 Heat-Shock Proteins antagonists & inhibitors, Mitochondrial Proteins antagonists & inhibitors
- Abstract
Breast cancer is one of the most serious cancers worldwide, and chemotherapy resistance frequently drives cancer progression. Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis given its resistance to chemotherapy. In our previous study, we found a remarkable abnormal methylation modification of the PCDHGB7 gene in breast cancer. However, the roles of PCDHGB7 in the progression and treatment of breast cancer are unclear. In this study, we examined the effects of PCDHGB7 on the sensitivity of TNBC cells to carboplatin and investigated the underlying mechanism. By knocking down and overexpressing PCDHGB7 in HS578T and BT549 cells, we confirmed that PCDHGB7 increases TNBC cell chemosensitivity to carboplatin. Mechanistically, we found that PCDHGB7 negatively regulates the expression of HSPA9, uplifting its inhibition on P53 translocation and caspase-3 activation. Thus, we demonstrated that PCDHGB7 increases chemosensitivity of TNBC cells to carboplatin by inhibiting HSPA9 via inducing apoptosis. PCDHGB7 and HSPA9 represent potential therapeutic targets for chemosensitivity in breast cancer.
- Published
- 2019
- Full Text
- View/download PDF