The Antagonism Of Atractylenolide I On Paclitaxel Increasing Interleukin 6(IL-6) Secretion And Chemoresistance In Ovarian Cancer Cell

Objective:To study the antagonism of atractylenolide I (AO-I) on paclitaxel (PTX) increasing interleukin-6(IL-6) secretion in epithelial ovarian cancer cell and chemo-resistance.Methods:Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in supernatant solution. The inhibitory effects of atractylenolide I, paclitaxel and paclitaxel co-treatment with AO-I on the growth of SKOV-3 cell and A2780 cell were investigated by using MTT assay, and the IC50's were calculated as a curvilinear regression equation.Results:①In (MyD88+)SKOV-3 cell lines, the cells produce IL-6. Paclitaxel and LPS induced a significant increase in IL-6 production in a dose-dependent and time-dependent manner (P< 0.05). AO-I in low concentration did not affect IL-6 levels,(P >0.05) but could depress IL-6 levels in high concentration(P< 0.05). AO-I also antagonize paclitaxel increased secretion of IL-6. Expression of TLR-4/MyD88 in EOC cells is necessary for IL-6 in these effects;②AO-1 almost did not show inhibition of SKOV-3 cells and A2780 cells survival, but PTX could inhhibits the growth of these cells in does-dependent, the IC50's were (0.038±0.0042)μmol/L and (0.034±0.0035)μmol/L; AO-1 enhanced the cytotoxicity of PTX to SKOV-3 cells, and the IC50's of PTX in co-treatment with AO-I (100μmol/L) declined to (0.011±0.0040)μmol/L (P< 0.05). In A2780 cells, there is no change in the IC50 (0.027±0.0057μmol/L) of PTX in co-treatment with AO-Ⅰ(100μmol/L) compare with the IC50 of PTX (P>0.05)Conclusion:AO-Ⅰantagonize the effect of PTX increasing IL-6 secretion in EOC cells, and high concentrations of AO-Ⅰcould depress the EOC cells secret IL-6 directly; AO-I does not affect growth of EOC cells but induce the responsiveness of EOC cells to PTX. All these effects depend on the expression of TLR-4/MyD88+ in EOC cells.