Figure 1.
Concomitant treatment of PTXs + BIBFs significantly inhibited cell growth only in EC cells with LOF p53 mutations. (a) Three EC cell lines were treated with PTXs and/or BIBFs for 72 h: Ishikawa cells; 5 nM PTXs and 2.5 μM BIBFs, Hec50co cells; 5 nM PTXs and 2.5 μM BIBFs, and KLE cells; 10 nM PTXs and 2.5 μM BIBFs. All combinatorial treatments were concomitant. (b) Sequential and concomitant treatments were also evaluated using Hec50co cells. PTXs and BIBFs doses were the same as in (a). The first treatment was added for 48 h, washed away, and then the second treatment was added for an additional 72 h. The untreated control group was incubated with fresh media for 5 days. (c) Synergy between PTXs and BIBFs was evaluated in Hec50co cells. Left panel represents dose response curves of PTXs, BIBFs or the combination using varied concentrations of PTXs with either 1 µM BIBFs or 100 nM BIBFs for 72 h. Right panel represents combination index (CI) vs. fraction affected (Fa) curve; CI<1 indicates synergy. Cytotoxicity was determined using the MTS assay. Statistical analysis for panels A and B was performed using one-way ANOVA with Tukey post hoc test. Data are expressed as mean ± SEM (n=3). *** p<0.001, * p<0.05.