Neoplasma Vol.62, No.2, p.209-229, 2015
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| Title: Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer |
| Author: X. GAO, Y. ZHOU, K. X. WU, Y. H. DING, D. M. FAN, M. YANG, Y. Z. ZHANG, Y. J. ZHANG, D. S. XIONG |
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Abstract: 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.
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| Keywords: PHII-7, invasion, migration, multidrug resistance, epithelial-mesenchymal transition |
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Published online: 14-Jan-2015
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| Year: 2015, Volume: 62, Issue: 2 |
Page From: 209, Page To: 229 |
doi:10.4149/neo_2015_026
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