Figure 1. Expression of the VEGF family in the EOC cells.

(A,B). Higher expression of VEGFA, VEGFC, VEGFD, VEGFR1 and VEGFR2 was observed in the multidrug-resistant OVCAR3, SKOV3 and A2780CP cells compared to the chemosensitive cell lines. Gene expression levels were normalized to HPRT1 (C) Correlation of VEGFR2 expression with resistance to cisplatin. EOC cell lines with higher expression of VEGFR2 showed significantly higher cisplatin IC₅₀ values. (D) The effect of the time-sequenced apatinib-cisplatin therapy on cell proliferation was investigated by MTT assay and shown by IC₅₀ shift analysis. The cultures were pre-treated with apatinib (10 μM) followed by treatment with cisplatin (0.1, 0.5, 1, 2.5, 5 and 10 μg/mL) for 48 h. (E) The effect of apatinib-cisplatin therapy on cell viability was demonstrated by crystal violet staining. The cells were pre-treated with apatinib (10 μM) followed by treatment with 0.1 μg/mL of cisplatin for 48 h. The cultures were stained with crystal violet and imaged by an inverted microscope (images acquired at 10x magnification). (F) Normalised isobolograms of combination of apatinib and cisplatin. The data were analysed using the CalcuSyn software. The connecting line represents additivity. Data points located below the line indicate a synergistic drug-drug interaction and data points above the line indicate an antagonistic interaction. The numbers under the isobolograms indicate the doses of cisplatin and apatinib in combination. (G) Association of VEGFC expression and resistance to erlotinib. Higher expression of VEGFC (r = 0.93, P = 0.02) positively correlated with resistance to erlotinib. (H) The effect of exogenous VEGFC on proliferative response to erlotinib was determined by MTT assay. Caov4 cells were pre-treated with human recombinant VEGFC (rVEGFC) for 4 h, followed by treatment with erlotinib for 48 h. Data are given as mean ± SD. Statistically significant values of *p < 0.05, **p < 0.01, and ***p < 0.001 were determined compared with the control.