Abstract:

Objective     To investigate the role of the PARP-1 gene in the mechanism of chemoresistance in ovarian cancer, and to study the reverse effect of silencing PARP-1 by RNA interference on cisplatin(CDDP)-resistance of C13* cells.  Methods     Expressions of PARP-1 mRNA and protein in C13* and OV2008 cells were detected by real-time fluorogenic quantitative PCR (RFQ-PCR) and Western blot, respectively. RFQ-PCR and Western blot were also used to validate whether the PARP-1 gene was silenced. The influence of siRNA on cellular sensitivity to CDDP and cell proliferation activity was detected by MTT assay. Results    The PARP-1 mRNA and protein levels in C13* cells were (2.12±0.97) and (1.89±0.23) fold of those in OV2008 cells (P<0.05). PARP1siRNA significantly down-regulated PARP-1 mRNA and protein levels (P<0.05). mRNA and protein expressions of PARP-1 were decreased by (71.23±5.41)% and (73.84±3.78)%, respectively(P<0.05). The inhibitory concentration 50%(IC50) of CDDP was decreased by (89.77±10.06)% (P<0.05), and proliferation activity of C13* cells was inhibited (P<0.05).  Conclusion      Expression of the PARP-1 protein in ovarian cancer cell lines is related to cellular sensitivity to CDDP. PARP1siRNA treatment can significantly down-regulate PARP-1 expression in transcriptional and translational levels, and effectively reverses resistance of C13* cells to CDDP.

Key words: Ovarian neoplasms; Small interfering RNA; Drug resistance， neoplasms; Genes, PARP-1