Research Of Gleevec (Imatinib) On Proliferation Of Human Ovarian Cancer Cell Line SKOV-3

Objective The purpose of this research was to detect the expression of imatinib target receptor on human ovarian cancer cell line SKOV-3 and to explore the effects of imatinib on proliferation and sensitivity to cisplatin and paclitaxel on human ovarian cancer cell line SKOV-3. To observe the inhibitory effect of imatinib on PDGFR phosporylation in vitro and explore the mechanism of its anti-tumor cells and the sensitizing effect of chemotherapy for clinical treatment of ovarian cancer with imatinib providing experimental basis.Methods MTT assay was used to analyze growth inhibitory effect of imatinib on SKOV-3 cells; cell apoptosis was determined by Hoechst33342 fluorescence; Adopt the Immunofluoresence to detect the expression of p-PDGFRβbefore and after treatment of imatinib.Results 1. Imatinib inhibited the human ovarian cancer cell SKOV-3 growth in a concentration-dependent manner, with the increase of drug concentration, cell proliferation inhibition rate increased. Compared with the control group, the difference was statistically significant (P<0.05).2. Hoechst fluorescence detect that Imatinib could induce the SKOV-3 cell apoptosis,and a small concentration (5μmol/L) induced more apoptotic cells compared with medium and high concentration group.3. When different concentrations of imatinib combined with classical chemotherapy drugs cisplatin and paclitaxel, the cell inhibition rate increased with the increasing concentration of imatinib, and the inhibition rate were higher than imatinib alone (P<0.05). In SKOV-3, imatinib showed the greatest synergistic effect with the two cytotoxic drugs at 5μmol/L.4. Based on the above results, we have chosen imatinib 5μmol/L as a sensitizing concentration of cisplatin and paclitaxel, results showed that: imatinib significantly enhanced the sensitivity to cisplatin and paclitaxel (P<0.05), especially when cisplatin and paclitaxel in a small concentration.5. In the absence of ligand stimulation, PDGFRβare present as unphosphorylated, inactive monomers in the cell membrance. Immunofluorescence results showed that: the normal SKOV-3 cells were grown for 24 hours in the absence of serum medium to express only a small amount of p-PDGFRβ,fluorescence is extremely weak; After stimulation with the growth factor PDGF-BB100ng/mL,we can see the bright green fluorescence in the membrane and cytoplasm;cells after imatinib treatment,p-PDGFRβexpression is difficult to capture. Summary, imatinib can block the PDGFRβphosphorylation in vitro.Conclusions Imatinib has an killing effect on human ovarian cancer cell line SKOV-3 and enhance the sensitivity to cisplatin and paclitaxel significantly. Imatinib can block the expression of p-PDGFRβinduced by PDGFBB on SKOV-3 cells, This might be one of the ways that imatinib impact on cell proliferation and play a role of sensitizing effect.