期刊
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
卷 37, 期 5, 页码 1375-1388出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/147323000903700512
关键词
HUMAN OVARIAN CANCER CELLS (HO8910); HEAT SHOCK PROTEIN 27 (HSP27); PACLITAXEL; SMALL INTERFERING RNA (SIRNA); REACTIVE OXYGEN SPECIES; GENE EXPRESSION
资金
- Youth Foundation of the Second Affiliated Hospital of Harbin Medical University [QN200817]
Increasing evidence indicates that reactive oxygen species (ROS) are involved in paclitaxel cytotoxicity. Modulating the oxidant-antioxidant status of tumour cells may increase the antitumour activity of paclitaxel. The cytoprotective roles of heat shock protein 27 (HSP27) include chaperoning cellular proteins, regulating apoptotic signalling and modulating oxidative stress. Immunohistochemical staining for HSP27 in human ovarian cancer specimens showed HSP27 was associated with aggressive malignant ovarian disease. Small interfering RNA (siRNA) was used to down-regulate HSP27 in human ovarian cancer cells (HO8910). Reduction of HSP27 expression increased the in vitro chemosensitivity of HO8910 cells to paclitaxel and increased paclitaxel-induced apoptosis and ROS production, although the ROS scavenger, N-acetyl-L-cysteine, partly offset the effects of HSP27 siRNA. Thus, gene knock-down of HSP27 offsets the role of this protein in resisting oxidant stress, thereby indirectly increasing the sensitivity of cells to paclitaxel. The siRNA-induced knock-down of HSP27 could be a novel and potent strategy to help overcome chemotherapeutic resistance to paclitaxel in epithelial ovarian cancer cells.
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