| Objective Cisplatin(cis-diamminedichloroplatinum Ⅱ, CDDP) is one of the most effective chemotherapeutic agents and is widely used in the treatment of cervical cancer(CC), but cancer cell acquired resistance to this drug during the course of its treatment. The aim of this study was to investigate the role of cyclin Ⅰ to cisplatin resistance in CC cell.Methods Cervical tumor specimens from 30 patients were recruited in this study. We analyzed the expression of cyclin Ⅰ by real-time polymerase chain reaction(q RT-PCR), Western blotting examination of downstream effectors.Cell proliferation assay and xenograft experiments were performed for cisplatin cytotoxicity assay. Lentivirus-mediated and si RNA-mediated genes overexpression or knockdown was applied to investigate the role of cyclin Ⅰ to cisplatin resistance in CC cell.Results We found that high level of cyclin Ⅰ was associated with cisplatin resistance in CC.Here, we described that cyclin Ⅰ protein becomes highly expressed in human CC patients resistant to cisplatin chemotherapy. Stable overexpressed cyclin Ⅰ promotes Hela cell resistanceto higher concentrations of cisplatin.in addition, upregulated level of cyclin Ⅰ increased tumor cells growth in vitro and enhanced tumor resistance to cisplatin in vivo.The further mechanism investigated showed that cyclin Ⅰ upregulated the expression of cyclin-dependent kinase 5(Cdk5) promoting cisplatin resistance bypreventing apoptosis in CC cell line. Consistently, the cyclin Ⅰ overexpressed Hela cell lines produce increased sensitivity to cisplatin treatment through knockdown of Cdk5 protein with siRNA.Conclusions Cyclin Ⅰ and its downstream protein Cdk5 are associated with the cisplatin-resistace of cervical cancer cells.Further studies showed that the upregulation of cyclin Ⅰ activated Cdk5,and Cdk5 promotes cisplatin-resistant via protects cells from apoptosis in cervical cancer. |
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