Effects and Mechanisms of Curcumol in Inhibiting Adipocyte-Induced ANGPTL4-Mediated Resistance to Carboplatin in Ovarian Cancer Cells
Objective:This study aimed to investigate the role and mechanism of adipocytes in carbo-platin resistance of ovarian cancer and explore the reversing effect of curcumol.Methods:The cytotoxic ef-fects of carboplatin and curcumol at different concentrations on SK-OV-3 ovarian cancer cells were deter-mined using the CCK-8 assay.The selected concentrations were then used for subsequent experiments.Co-culture of adipocytes and SK-OV-3 cells was performed using a 0.4 μm Transwell chamber to investigate the role of adipocytes in mediating carboplatin resistance in SK-OV-3 cells.The levels of angiopoietin-like protein 4(ANGPTL4)in the conditioned medium were measured using an enzyme-linked immunosorbent as-say(ELISA).The expression levels of ANGPTL4 mRNA in adipocytes and SK-OV-3 cells were determined by RT-PCR.Western blot analysis was performed to study the expression of resistance proteins induced by adipocytes in SK-OV-3 cells.Results:The half inhibitory concentration(IC50)of carboplatin on SK-OV-3 cells was 52.28 μmol·L-1,while the IC50 of curcumol on SK-OV-3 cells was 91.84 μg·L-1.The expression of ANGPTL4 mRNA in the conditioned medium from the co-culture of adipocytes and SK-OV-3 cells was significantly increased(P<0.01)and could be reversed by curcumol(P<0.01).Curcumol markedly reduced the expression of ANGPTL4 mRNA in adipocytes under co-culture conditions(P<0.01),without significantly affecting the expression in SK-OV-3 cells(P>0.05).The expression of resistance proteins in SK-OV-3 cells was significantly increased under co-culture conditions(P<0.01),and this effect could be reversed by curcumol(P<0.01).Conclusion:Co-culture of adipocytes and ovarian cancer cells can induce activation and secretion of ANGPTL4 protein,promoting resistance protein expression and carboplatin resistance in o-varian cancer cells,which can be reversed by curcumol.
Ovarian cancerAdipocytesAngiopoietin-like protein 4CarboplatinCurcumol
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