Effect of SCD1 Inhibitor on Proliferation and Apoptosis of Breast Cancer Cells and Related Mechanism

Abstract

Objective To investigate the expression of stearoyl-CoA desaturase-1 (SCD1) in breast cancer tissues, and to analyze the effect of inhibiting SCD1 activity on the growth and apoptosis of breast cancer MCF-7 cells and related mechanism. Methods We constructed tissue microarray and then the expression of SCD1 proteins were detected by immunohistochemistry techniques in breast cancer and normal breast tissues. The viability of MCF-7 cells treated with MF-438 was measured using MTS assay. Apoptosis morphology was observed by fluorescence microscope after Hoechst 33342 staining and the apoptotic index was calculated. Cell apoptosis was determined by flow cytometry after PI staining. The expressions of Bcl-2 and Bax proteins were examined by Western blot. Results The positive rate of SCD1 expression in breast cancer tissues was significantly higher than that in normal breast tissues (P < 0.05), and SCD1 levels were lower in triple-negative breast cancers than those in other subtypes (P < 0.05). MF-438 showed a significant dose-dependent proliferation inhibition in MCF-7 cells in 0.1-100μmol/L. The typical apoptotic morphology was observed in MCF-7 cells treated with 5μmol/L MF-438 for 48h; the apoptotic index and apoptosis rate were significantly higher than those in the control group(P < 0.05); meanwhile, the expression of anti-apoptotic protein Bcl-2 was down-regulated and the expression of pro-apoptotic protein Bax was up-regulated. Conclusion Inhibition of SCD1 could inhibit the proliferation and induce the apoptosis of breast cancer cells. Further research on SCD1 is expected to provide a new target for molecular targeted therapy of breast cancer.

Keywords

• breast cancer
• scd1
• fatty acid metabolism
• proliferation
• apoptosis