Effect of isorhamnetin on carbonic anhydrase IX expression and tumorigenesis of bladder cancer by activating PPARγ/PTEN/AKT pathway

Abstract

Background: To clarify the research prospect and mechanism analysis of isorhamnetin as a therapeutic drug for bladder cancer.

Methods: Firstly, the effects of different concentrations of isorhamnetin on the expression of PPARγ/PTEN/Akt pathway protein, CA9, PPARγ, PTEN and AKT protein were discussed by western blot. The effects of isorhamnetin on the growth of bladder cells were also analyzed. Secondly, we verified whether the effect of isorhamnetin on CA9 was related to PPARγ/PTEN/Akt pathway by western blot, and the mechanism of isorhamnetin on the growth of bladder cells is related to this pathway by CCK8, cell cycle and ball formation experiment. Further, nude mouse model of subcutaneous tumor transplantation was constructed to analyze the effects of isorhamnetin, PPAR and PTEN on 5637 cell tumorigenesis and the effects of isorhamnetin on tumorigenesis and CA9 expression through PPARγ/PTEN/Akt pathway.

Results: Isorhamnetin inhibited the development of bladder cancer, and regulated the expression of PPAR, PTEN, AKT, CA9. Isorhamnetin inhibits cell proliferation and the transition of cells from G0/G1 phase to S phase, and tumor sphere formation. Carbonic anhydrase IX is a potential downstream molecule of PPARγ/PTEN/AKT pathway. Overexpression of PPARγ and PTEN inhibited expression of CA9 in bladder cancer cells and tumor tissues. Isorhamnetin reduced CA9 expression in bladder cancer via PPARγ/PTEN/AKT pathway, thereby inhibiting bladder cancer tumorigenicity.

Conclusion: Isorhamnetin has the potential to become a therapeutic drug for bladder cancer, whose antitumor mechanism is related to PPARγ/PTEN/AKT pathway. Isorhamnetin reduced CA9 expression in bladder cancer via PPARγ/PTEN/AKT pathway, thereby inhibiting bladder cancer tumorigenicity.

Keywords: Bladder cancer; Carbonic anhydrase IX; Isorhamnetin; PPARγ/PTEN/AKT pathway.