The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell

Current Pharmaceutical Biotechnology
Xinyan ChenYongjie Tian

Abstract

Many targeted ovarian cancer patients are resistant to olaparib treatment. Here we seek to understand the underlying molecular events and search for potential combinational therapeutics to surmount the intrinsic olaparib resistance in human ovarian cancer. The cytotoxicity was determined by the MTT assay and cell viability was measured using Cell Counting Kit-8 (CCK-8). Protein expressions of ERK, P38, JNK, ERK5, LC3, N-CADHERIN, α-SMA were determined by western blotting. The invasion capacity was evaluated by the transwell chamber. Autophagy flux was monitored by the LC3 puncta formation. The epithelial-mesenchymal transition (EMT) markers were profiled by immunoblotting detection. The in vivo tumor progression was determined by xenograft mice model. The olaparib-resistant cell lines were successfully generated in both SKOV3 and A2780 cells. The proliferative index was significantly higher in resistant cells in comparison with sensitive counterparts in the presence of olaparib. Both P38 and JNK were up-regulated in olaparib-resistant cells. The combinational treatment with P38-specific inhibitor SB202190 and JUN-specific inhibitor SP600125 significantly suppressed cell growth and migration, which was further attributed to the ...Continue Reading

Citations

Feb 23, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zeen WuRenjun Pei
Aug 10, 2021·Environmental Science and Pollution Research International·Lina ZhouYinyan He

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