Fig. 6

MerTK inhibition sensitized MCL cells to common chemotherapeutic agents. a, b MerTK knockdown sensitized MCL cells to vincristine and doxorubicin in vitro. Z-138 and Mino cells pre-infected with shControl or shMerTK were treated with indicated concentrations of vincristine (a) or doxorubicin (b) for 72 h. Inhibition rates were calculated as that in Fig. 3b. Mean values and SEs were derived from three independent experiments. **P < 0.01; ***P < 0.001. c, d UNC2250 increased the cytotoxic effect of vincristine and doxorubicin in vitro. Z-138 and Mino cells were treated with indicated concentrations of vincristine (c) (or doxorubicin (d)) alone, UNC2250 alone, or combination of vincristine (or doxorubicin) and UNC2250 for 72 h. Inhibition rates were calculated as that in Fig. 3b. The combination index values (CI) were calculated using CalcuSyn software. + slight synergism (CI 0.85–0.90); ++ moderate synergism (CI 0.7–0.85); +++ synergism (CI 0.3–0.7). e, f UNC2250 provided additional therapeutic benefit in combination with doxorubicin rather than vincristine in vivo. Tumor size curves derived from Z-138 xenograft mouse model treated with UNC2250 in combination with doxorubicin (e) or vincristine (f). Mean values and SEs were derived from each treatment arm (n = 6). *P < 0.05; **P < 0.01; ****P < 0.0001. (Blue asterisks denote comparison between vehicle and UNC2250 monotherapy, green asterisks denote comparison between indicated treatment and combination therapy, and red asterisks denote comparison between UNC2250 and combination therapy)