Molecular Mechanisms of Adriamycin Hypersensitivity in Human Breast Carcinoma MCF-7/adr Cells by Targeting Silence of Chkl

Abstract: Our aim is to investigate effects on proliferation and cell cycle of human breast carcinoma MCF-7/adr cells resistant to adriamycin and explore the mechanisms of adriamycin hypersensitivity by targeting silence of Chk1. The siRNA targeting at Chkl gene was transfected into MCF-7/adr cells. The protein expression of Chkl was detected by Western blot．The MCF-7/adr cells were divided into three groups: untransfection， lipofectamine and Chkl siRNA-transfected group．After being treated with adriamycin， cell proliferation and cell cycle were determined by MTT assay and flow cytometry．The Chkl expression at protein levels in Chk1 siRNAtransfected group was reduced by about 67% compared with untransfection， lipofectamine group (P<0.05)．Inhibition of the Chkl expression in Chkl siRNA-transfected group significantly abrogated G2/M arrest induced by adriamycin， and the proportion of the cells in G2/M phase was lower than that in other two groups and increased cell apoptotic rates from (5.54±0.15)% to (22.24±0.13)% (P<0.05)．After being Treated with 0.4 mg/L or 4 mg/L of adriamycin， cells-transfected proliferation rate was decreased by 13% or 34% respectively. siRNA targeting at Chkl gene can effectively inhibit the Chkl expression in MCF-7/adr cells， which enhanced the drug sensitivity of MCF-7/adr cells to adriamycin through blocking the signal transduction pathways of cell cycle checkpoint. So Chkl gene silence may provide a new target and an effective way against drug resistance of breast cells.

CSTR: 32200.14.cjcb.2011.05.0011