Effect of baicalein on the inhibitory role of cisplatin on the proliferation of ovarian cancer A2780 cells

Objective To evaluate the effect and mechanism of baicalein on the inhibitory role of cicplatin on the proliferation of ovarian cancer A2780 cells. Methods The A2780 cells in the logarithmic growth phase were selected. The cytotoxicity of baicalein on the ovarian cancer A2780 cells was assessed by CCK-8 assay. The difference of IC₅₀ of cisplatin in the A2780 cells treated with and without baicalein was statistically compared. After the treatment with cell gap junction （GJ） pathway inhibitor 18-α-glycyrrhetinic acid （18-α-GA）, the effect of cisplatin on the inhibitory rate of A2780 cells was evaluated. The effect of baicalein treatment on the inhibitory role of cisplatin was assessed. The impact of baicalein on the function of GJ signaling pathway in the A2780 cells was evaluated by Parachute assay. Based on the GEO dataset, the expression levels of GJA1 （Cx43） genes between the normal ovarian epithelial and ovarian cancer epithelial tissues were statistically compared. The effect of baicalein on the expression of Cx43 protein in the A2780 cells was assessed by Western blot. The targeted protein of baicalein was predicted by Swiss Target Prediction database. The interaction network between the targeted proteins and GJ pathway was constructed. Results Baicalein treatment at a dose of≤10 μmol/L provoked no obvious toxicity to the A2780 cells. Compared with cisplatin alone, baicalein treatment at a dose of 10 μmol/L could significantly increase the inhibitory rate of cisplatin on the A2780 cells （P < 0.01）. Administration of 18-α-GA could considerably lower the inhibitory rate of cisplatin on the A2780 cells and significantly reverse the sensitization effect of baicalein on cisplatin （both P < 0.01）. GEO dataset revealed that the expression level of Cx43 mRNA in the ovarian cancer epithelial tissues was significantly lower compared with that in the normal ovarian epithelial tissues （P < 0.05）. Treatment with baicalein could significantly up-regulate the expression level of Cx43 protein （P < 0.01）. Swiss Target Prediction database demonstrated that baicalein directly targeted to the four proteins in the GJ pathway. Conclusion Baicalein can increase the cytotoxicity of cisplatin upon the ovarian cancer A2780 cells, probably correlated with the enhancement of the function of GJ pathway in the A2780 cells.