ºÚÁÏÍø

Abstract

New platinum complexes with different carrier ligands are developing to overcome the intrinsic or acquired resistance of the tumors during the therapy. A series of novel dinuclear platinum complexes based on the bisphosphonate ligands have been synthesized and characterized. For the purpose of discovering the pharmacology and action mechanism of this kind of compounds, the most potent compound [Pt(en)]2ZL was selected for systematic investigation of the underlying mechanisms accounting for their anticancer activity. In this study, the human gastric cancer cell lines SGC7901 were selected to investigate the anticancer effects of [Pt(en)]2ZL on this type of cancer cells. The MTT assay and colony formation assay were used to test the effect of [Pt(en)]2ZL on the cell viability and proliferation, respectively. The senescence-associated �²-galactosidase staining and immunofluorescence staining were also performed to assess the cell senescence and microtubule polymerization. Fluorescence staining and flow cytometry (FCM) were used to monitor the cell cycle distribution and apoptosis, and the expressions of related proteins were further detected with Western blot. [Pt(en)]2ZL exerted profound cytotoxic and antiproliferative effects on SGC7901 cells, and it also induced cell senescence and abnormal microtubule assembly, indicating the progress of mitotic catastrophe. Cell cycle arrest and apoptosis induced by [Pt(en)]2ZL were observed with FCM and fluorescence staining. The expressions of cell cycle regulators (p53, p21, cyclin D1, cyclin E and CDK2) and apoptosis-related proteins (Bcl-2, Bax, caspase 3, PARP and survivin) were mediated by [Pt(en)]2ZL, resulting in the cell cycle arrest and apoptosis. Therefore, [Pt(en)]2ZL exerted antitumor effect via the cell cycle arrest in the G1/S phase and the induction of apoptosis.

Biography

Email: xieminhao@jsinm.org