Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy
Fig 7
Effects of Pim inhibitors on Echinococcus larvae and human cells.
(A) Heat map showing the effects of 20 in silico screen compounds on MV. Different concentrations (indicated below) of each compound (indicated to the left) were incubated in vitro with MV for 28 d and structural integrity was assessed. Colour-code indicating percentages of surviving vesicles is indicated below. (B) Effects of four in silico screen compounds on MV production from PC. 10 μM of each compound (indicated below) were incubated for 21 d with PC in vitro and the production of MV was assessed. For comparison, SGI-1776 was tested at 10 μM. Error bars represent standard deviation. Kruskal-Wallis test followed by Dunn’s multiple comparison test was used for comparisons with the control (DMSO) group. (C) Effects of Z196138710 and SGI-1776 on MV. Both compounds were tested at different concentrations (shown below) on MV in vitro. Structural integrity was measured after 28 d. Error bar represents standard deviation. One was ANOVA followed by Dunnet’s multiple comparison test was used in comparisons with control (DMSO) group. p values less than 0.0001 are summarized with **** and p values less than 0.0332 are summarized with *. (D) Effects of Z196138710 and SGI-1776 on the in vitro formation of MV from PC. Both inhibitors were incubated at different concentrations (indicated below) for 21 d with PC and the formation of mature MV was measured. Error bar represents standard deviation. Kruskal-Wallis test followed by Dunn’s multiple comparison test was used in comparisons with control (DMSO) group. * represents p ≤ 0.0332. (E) Effects of Z196138710, SGI-1776, and CX-6258 on human HEK293T cells. HEK293T cells were incubated with different concentrations of inhibitors as indicated below. Cell viability was measured after 3 d. (F) Effects of inhibitors on human HepG2 cells. For experimental procedure, see (E). Error bar represents standard deviation. Tukey’s multiple comparison test followed by one way ANOVA was used to compare all experimental settings, only comparisons for equal inhibitor concentrations are shown. P values less than 0.0001 are summarized with **** and p values less than 0.0021 are summarized with **.