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Archive > Volume 21 Issue 3 > 2014,21(3):269-274. DOI:10.3872/j.issn.1007-385X.2014.03.006 Prev Next
Basic Research
hSulf-1overexpression enhance the sensitivity of breast cancer MCF-7 cells to the PARP inhibitor AZD2281
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Abstract:
To investigate the possibility of enhance the sensitivity of breast cancer MCF-7 cells to the PARP inhibitor AZD2281 by up-regulate the expression of hSulf-1. Methods: MCF-7 cells were infected with Ad5-hSulf1 or Ad5-EGFP. Transfectants were treated with different concentrations of AZD2281 and the most optimal concentration was determined. In further experiments, both Ad5-hSulf-1-overexpressing MCF-7 cells and Ad5-EGFP-expressing control MCF-7 cells were treated with AZD2281 at the optimal concentration determined. After treatment for 24 h, cell cycle progression was assessed by flow cytometry (FCM), formation ability of MCF-7 cells by colony formation assay, protein levels of cyclin dependent kinase 4 (CDK4) and phosphorylated protein kinase B (p-AKT) Western blotting, cell migration by Transwell assay, and proliferative ability by MTT assay. Results: AZD2281 showed the peak inhibitory activity at a concentration of 7 μmol/L. When this concentration was used,Ad5-EGFP-expressing MCF-7 cells showed significant increased in the proportion of G2/M phase cells ([22.15±0.17]% vs [17.44±0.57]%, P<0.01), the colony formation ability ([21.43±1.52]% vs [49.43±1.44]%, P<0.01 ), levels of cell cycle protein CDK4 (0.67±0.02 vs 0.72±002, P<0.01) and p-AKT (0.17±0.003 vs 0.42±0.02, P<0.01), and the rateof migration ([57.69±483]% vs [79.35±5.44]%, P<0.01) and proliferation (10.33±1.53 vs 50.67±2.31, P<0.01), as compared with MCF-7 cells expression Ad5- hSulf-1. Conclusion: The overexpression of hSulf-1 may significantly increase the chemosensitivity of MCF-7 cells to AZD2281, induce ell cycle arrest at G2/M-phase and inhibit cell proliferation and migration capacities, possibly through regulation of CDK4 expression and AKT phosphorylation.
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Project Supported:
Project supported by the National Natural Scientific Foundation of China (No. 81370552, No.81172303, No. 81172019)
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