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

In: NEOPLASMA, vol. 62, no. 2
X. Gao - Y. Zhou - K. Wu - Y. Ding - D. Fan - M. Yang - Y. Zhang - D. Xiong
Detaily:
Rok, strany: 2015, 209 - 229
O článku:
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
Ako citovať:
ISO 690:
Gao, X., Zhou, Y., Wu, K., Ding, Y., Fan, D., Yang, M., Zhang, Y., Xiong, D. 2015. Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer. In NEOPLASMA, vol. 62, no.2, pp. 209-229. 0028-2685.

APA:
Gao, X., Zhou, Y., Wu, K., Ding, Y., Fan, D., Yang, M., Zhang, Y., Xiong, D. (2015). Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer. NEOPLASMA, 62(2), 209-229. 0028-2685.