Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer.

Abstract

UNLABELLED:

PHII-7, a derivative of indirubin, showed significant anti-cancer activities in vivo and in vitro. We asked whether treating human metastatic cancers and multidrug resistant cancer with PHII-7 would inhibit their invasion and migration. Cell growth was tested by MTT assay and colony formation assay. Apoptosis was examined by flow cytometry. Transwell-based assay and wound healing assay were used to examine cell invasion and migration. Real-time PCR assay and western blot assay were performed to test gene expression on mRNA and protein level, respectively. Firstly, we confirmed that MCF-7/ADR cells showed more invasive and migratory properties compared with MCF-7 cells which were associated with several EMT markers, such as E-cadherin, Slug and vimentin. Secondly, we found that slightly toxic doses of PHII-7 decreased the number of cells that invaded a model epithelial basement membrane and that migrated by switching the molecular signature of the cells from mesenchymal to epithelial. And PHII-7 significantly regulated expression of several epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin, Slug, β-catenin and vimentin. Thirdly, compared with control, PHII-7 inhibited cell proliferation in a time- and dose-dependent manner. Higher doses of PHII-7 also induced apoptosis through activating PARP, caspase-9 and caspase-3. PHII-7 significantly inhibited invasion and migration in both metastatic cancers and multidrug resistant cancer. Our results may provide several data for future application of PHII-7 on drug design and patients treatment.

KEYWORDS:

PHII-7, invasion, migration, multidrug resistance, epithelial-mesenchymal transition.

• Authors: X Gao, Y Zhou, K X Wu, Y H Ding, D M Fan, M Yang, Y Z Zhang, Y J Zhang, D S Xiong
• Journal: Neoplasma (Neoplasma) 2015 Vol. 62 Issue 2 Pg. 209-29 ISSN: 0028-2685 [Print] Slovakia
• PMID: 25591586 (Publication Type: Journal Article)