SCD1抑制剂对乳腺癌细胞增殖凋亡的影响及其机制

目的 检测硬脂酰辅酶A去饱和酶1（stearoyl-CoA desaturase 1, SCD1）在乳腺癌组织中的表达，分析抑制SCD1的活性对乳腺癌MCF-7细胞增殖凋亡的影响及其机制。方法 采用免疫组织化学法检测乳腺癌及癌旁正常组织中SCD1蛋白的表达。应用MTS法测定SCD1抑制剂MF-438对MCF-7细胞增殖的抑制率。应用Hoechst33342染色荧光显微镜观察细胞形态并计算凋亡指数，PI染色流式细胞术检测细胞凋亡率。蛋白质印迹法检测凋亡相关蛋白Bcl-2和Bax的表达。结果 乳腺癌组织中SCD1阳性表达率显著高于正常乳腺组织（P<0.05），并且三阴性乳腺癌中的SCD1表达水平低于其他亚型（P<0.05）。MF-438在0.1~100 μmol/L浓度范围内，对MCF-7细胞显示出显著的剂量依赖性的增殖抑制作用，并在低血清条件下更为敏感。MCF-7细胞在5 μmol/L MF-438作用48 h后，表现出典型的细胞凋亡特征性变化，细胞凋亡指数及细胞凋亡率显著高于对照组（P<0.05）；同时，MF-438下调MCF-7细胞抑凋亡蛋白Bcl-2的表达，并上调促凋亡蛋白Bax的表达。结论 抑制SCD1能抑制乳腺癌细胞增殖并诱导凋亡，对SCD1的深入研究将有望为乳腺癌的分子靶向治疗提供一个新的靶标。

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

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 triplenegative 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.