Multikinase inhibitor motesanib enhances the antitumor effect of cisplatin in cisplatin‑resistant human bladder cancer cells via apoptosis and the PI3K/Akt pathway

Oncology Reports
Jin-Nyoung HoSangchul Lee

Abstract

Motesanib (AMG 706) is a small organic molecule that acts as a multi‑targeted tyrosine kinase inhibitor of VEGF, PDGF and stem cell factor receptor. It exhibits a potent antitumor effect in vitro and in vivo. To investigate the anticancer effect and possible mechanisms of motesanib in cisplatin‑resistant human bladder cancer cells (T24R2), T24R2 cells were treated with motesanib (50 µM) with or without cisplatin (2.5 µg/ml). Cell growth was assessed by the Cell Counting Kit‑8 and clonogenic assays. Cell cycle progression and apoptotic cell death were examined using flow cytometry. The expression levels of apoptosis‑ and survival‑related proteins were determined by western blot analysis. In combination with cisplatin, motesanib exhibited synergistic inhibition on T24R2 cell growth. Treatment using motesanib in combination with cisplatin markedly induced apoptosis and promoted cell cycle arrest in the S phase. It also increased the expression of apoptosis‑related genes including caspases, poly(ADP‑ribose) polymerase and cytochrome c, whereas it decreased the expression of survival‑related genes including p‑PI3K and p‑Akt. In conclusion, combination treatment with motesanib and cisplatin revealed a synergistically enhanced antican...Continue Reading

Citations

Oct 18, 2019·Current Molecular Pharmacology·Samira BahramiAmirhossein Sahebkar
May 30, 2019·Cancers·Masahiro Shibata, Mohammad Obaidul Hoque
Dec 11, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Donghao ShangYuting Liu

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