Preclinical assessment of the VEGFR inhibitor axitinib as a therapeutic agent for epithelial ovarian cancer

E. Sun Paik, Tae Hyun Kim, Young Jae Cho, Jiyoon Ryu, Jung Joo Choi, Yoo Young Lee, Tae Joong Kim, Chel Hun Choi, Woo Young Kim, Jason K. Sa, Jin Ku Lee, Byoung Gie Kim, Duk Soo Bae, Hee Dong Han, Hyung Jun Ahn, Jeong Won Lee

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4 Citations (Scopus)

Abstract

Axitinib, small molecule tyrosine kinase inhibitor, demonstrates anti-cancer activity for various solid tumors. We investigated anti-cancer effect of axitinib in epithelial ovarian cancer (EOC). We treated EOC cells (A2780, HeyA8, RMG1, and HeyA8-MDR) with axitinib to evaluate its effects on cell viabilty, apoptosis and migration. Western blots were performed to assess VEGFR2, ERK, and AKT levels, and ELISA and FACS to evaluate apoptosis according to axitinib treatment. In addition, in vivo experiments in xenografts using A2780, RMG1, and HeyA8-MDR cell lines were performed. We repeated the experiment with patient-derived xenograft models (PDX) of EOC. Axitinib significantly inhibited cell survival and migration, and increased apoptosis in EOC cells. The expression of VEGFR2 and phosphorylation of AKT and ERK in A2780, RMG1, and HeyA8 were decreased with axitinib treatment in dose-dependent manner, but not in HeyA8-MDR. In in vivo experiments, axitinib significantly decreased tumor weight in xenograft models of drug-sensitive (A2780), and clear cell carcinoma (RMG1) and PDX models for platinum sensitive EOC compared to control, but was not effective in drug-resistant cell line (HeyA8-MDR) or heavily pretreated refractory PDX model. Axitinib showed significant anti-cancer effects in drug-sensitive or clear cell EOC cells via inhibition of VEGFR signals associated with cell proliferation, apoptosis and migration, but not in drug-resistant cells.

Original languageEnglish
Article number4904
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

ASJC Scopus subject areas

  • General

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