6-Shogaol Inhibits Cell Growth And Expression Of Proinflammatory Cytokines In Ovarian Cancer SKOV-3 And A2780 Cells

Purpose:The objective of this study is to investigate the inhibitory effect of 6-shogaol to cell growth and expression ofproinflammatory cytokines in human ovarian cancer cells by studying the influence of secretion of cytokines (IL-6, IL-8, VEGF),proliferation, cycle and apoptosis of MyD88+human ovarian cancer cells(SKOV-3) and MyD88-human ovarian cancer cells(A2780) and the change of secretion of cytokines (IL-6, IL-8, VEGF) and proliferationof MyD88+human ovarian cancer cells(SKOV-3) and MyD88-human ovarian cancer cells(A2780) induced by6-shogaol and Paelitaxel.Method:1.The molecular docking of 6-shogaol and myeloid differentiation protein 2 (MD-2) was simulated by computer software.2.Theinhibitoryeffectsof 6-shogaol, Paelitaxel and 6-shogaol combination Paclitaxel on the growth of human ovarian cancer SKOV-3 cells and A2780 cells and the screening to concentration range of 6-shogaol were investigatedbyusingMTTassay.3.Enzyme-linked immunosorbent assay(ELISA) was used to detecte thesecretion levels of IL-6,IL-8 and VEGF in human ovarian cancer SKOV-3 cells and A2780 cells induced by 6-shogaol,Paelitaxel and 6-shogaol combination Paclitaxel.4.The effects of 6-shogaol and Paelitaxel at different concentrations on cell cycle distribution of human ovarian cancer SKOV-3 cells and A2780 cells and the effects of cells apoptosis rate of human ovarian cancer SKOV-3 cells and A2780 cells induced by 6-shogaol and Paelitaxel at fixed concentrations for different time,which were detected by using flowcytometry.Result:1.6-shogaol could be combined with MD-2 protein through the simulation of computer software to molecular docking.2.6-shogaol had obvious inhibition for the growth of human ovarian cancer SKOV-3 cells and A2780 cells.6-shogaol and paclitaxel could restrain the growth of these cells in dose-dependent manner and the 50% inhibitory concentration of 6-shogaol were(6.48±0.4536) umol/L and (6.21±0.3726) umol/L, the 50% inhibitory concentration of paclitaxel were(0.032±0.0026) umol/L and(0.027±0.0019) umol/L, respectively. 6-shogaol had no cell selecticity to MyD88+human ovarian cancer cells(SKOV-3) and MyD88-human ovarian cancer cells(A2780). The 50% inhibitory concentration of 6-shogaol were similar.6-shogaol had no synergistic inhibition to SKOV-3 cells and A2780 cells induced by paclitaxel(P>0.05).3.The SKOV-3 cells could secrete IL-6,IL-8 and VEGF and A2780 cells could secrete IL-8 and VEGF and hardly secrete IL-6.6-shogaol could reduce the secretion of IL-6,IL-8 and VEGF inSKOV-3 cells (P<0.05), but no effect on the secretion of IL-6,IL-8 in A2780 cells (P> 0.05).6-shogaol could reduce the secretion of VEGF in A2780 cells(P<0.05).Paclitaxel could induce the secretion of IL-6,IL-8 and VEGF inSKOV-3 cells (P<0.05), but no effect on the A2780 cells (P> 0.05).6-shogaol could reduce the secretion of IL-6,IL-8 and VEGF inSKOV-3 cells induced by Paclitaxel (P<0.05) and the secretion ofVEGF in A2780 cells by Paclitaxel(P<0.05), but no effect on the secretion of IL-6 and IL-8 inA2780 cells by Paclitaxel(P> 0.05).4.6-shogaol and paclitaxel could induce the apoptosis of SKOV-3 cells and A2780 cells in time-dependent manner(P>0.05).The cell cycle distribution of SKOV-3 cells and A2780 cells induced by 6-shogaol was not obvious(P>0.05), while cell cycle was arrested in G2/M phase by paclitaxel(P<0.05).Conclusion:1.6-shogaol might couldinhibitthe combination of MD-2 protein and TLR-4,which block the secretion ofproinflammatory cytokines in duced by LPS or paclitaxel and inhibit theinflammatory reactionaroundthe ovarian cancer cells.2.6-shogaol could induce the apoptosisof human ovarian cancer cells and had obvious growth inhibition to ovarian tumor.