Fig. 6

MSC activates the PI3K-AKT signaling pathway via TGF-β2 to promote drug resistance in GIST cells. Flow cytometry experiments showed that recombinant TGF-β2 reduced apoptosis in IM-treated GIST cells (A, B) and reduced G0/G1 phase cell ratio (C, D). Silencing of the TGF-β receptor and PI3K-AKT inhibitor antagonized this effect (A–D). CCK-8 assay showed that recombinant TGF-β2 increased the survival of GIST cells under IM treatment, and silencing of the TGF-β receptor and PI3K-AKT inhibitor antagonized this effect (E). Conditioned medium (CM) for MSC co-culture with GIST cells can partially restore the IC50 of IM inhibition of GIST proliferation (F). And recombinant TGF-β2 has similar effects to CM. But the addition of PI3K inhibitors Wortmannin counteracted this effect (G). After silencing the TGF- receptor on GIST cells, neither CM nor recombinant TGF-2 could increase the IC50 of IM to inhibit the growth of GIST cells anymore (H). All experiments were repeated at least thrice. Data are means ± SEM (n = 3 in each group) *p < 0.05; **p < 0.01