Marsdenia tenacissima extract enhances XXXX efficacy in @entity1149 xenografts.

@entity1 @entity8047 @entity4562 @entity5 @entity470 @entity19 @entity1149 @entity3963 @entity584 @entity3470 @entity1916 @entity1366 @entity9513
PURPOSE: The stem of Marsdenia tenacissima (Roxb.) Wight et Arn. has long been used as a medicine to treat @entity5 in China. Our previous in vitro results showed that Marsdenia tenacissima extract (MTE) overcomes @entity4562 resistance in @entity1149 ( @entity1149 ) cells. However, it is unknown whether MTE could enhance @entity4562 efficacy in vivo. The present study was intended to investigate the in vivo anti- @entity5 activity of MTE combined with @entity4562 . METHODS: @entity1 @entity1149 @entity1 (K-ras mutation) or H1975 cells ( @entity470 @entity9513 mutation) were subcutaneously inoculated into @entity19 . @entity5 volume and body weight were measured regularly. Resected @entity5 were weighed after the animals were sacrificed. Immunoblotting or immunohistochemistry was used to assess the cellular proliferation and apoptosis in xenograft @entity5 tissue. Expression of the @entity470 downstream pathways and @entity1916 were measured with western blot analysis to explore possible mechanisms. RESULTS: MTE (5, 10, 20  g/kg) dose-dependently reduced @entity5 growth and induced cell apoptosis. MTE suppressed @entity470 related signals, and 20  g/kg was the most effective dose. Low-dose MTE (5  g/kg) significantly enhanced @entity4562 efficacy in resistant H460 and H1975 xenografts. The combination inhibited @entity5 proliferation and induced cell apoptosis in both resistant @entity1149 xenografts. Constitutive activation of the PI3K/ @entity584 and @entity8047 / @entity3963 pathways is related to @entity470 -TKI resistance. Accordingly, phosphorylation of PI3K/ @entity584 / @entity3470 and @entity1366 was suppressed after combination treatment. Simultaneously, cross-talked @entity1916 and @entity470 were also prominently lowered in the presence of MTE combined with @entity4562 . CONCLUSION: The present results suggest that the combination of MTE and @entity4562 may be a promising therapeutic approach to enhance @entity4562 efficacy in resistant @entity1149 .
