白藜芦醇抑制耐阿霉素人乳腺癌细胞系MCF-7/ADM增殖的研究

Effects of resveratrol on proliferation in multidrug-resistant breast cancer line MCF-7/ADM

目的观察白藜芦醇对耐阿霉素人乳腺癌细胞系MCF-7/ADM增殖和细胞周期的影响及探讨其靶点蛋白质。方法采用四甲基偶氮唑盐(MTT)法、光学显微镜观察观察白藜芦醇对MCF-7/ADM细胞增殖的影响,流式细胞仪检测观察白藜芦醇对细胞周期的影响,Western blot法、亲和甄别磁珠法鉴定白藜芦醇的靶点蛋白质。结果白藜芦醇作用MCF-7/ADM 72 h之后,细胞增殖大量下降并且呈剂量依赖关系,而对正常肝细胞毒性很小。白藜芦醇可导致MCF-7/ADM细胞阻滞于G0/G1期。Cdk2、myosin和actin蛋白可能是白藜芦醇的靶点蛋白质之一。结论白藜芦醇可能是1种新发现的Cdk2的抑制剂,同时通过作用于细胞的骨架结构蛋白质来干扰细胞的有丝分裂过程,使细胞周期延长从而导致MCF-7/ADM的增殖受到抑制。提示白藜芦醇是1种活性强、低毒的抗癌化学前体分子。

Purpose To explore the effects of the resveratrol on the growth, and the cell cycles of the multidrug-resistant breast cancer cell line MCF-7/ADM and to study its binding proteins. Methods MTF method and the light microscopy were used to observe the effects of the resveratrol on the cell growth. FCM was used to examine the inductive effects of resveratrol on the cell cycles. Western blot and affinity beads analysis was confirmed to identify the binding protein of the resveratrol on the cell of MCF-7/ADM. Results It was manifested by MTF and the light microscopy that resveratrol could inhibit proliferation of the MCF-7/ADM significantly and in dose - dependent manner, but not human normal liver cell L-02. It was showed by FCM assay that resveratrol could inhibit the MCF-7/ADM to G0/G1 phase. It was discovered by Western blot and affinity beads assay that Cdk2, myosin and actin proteins might be the binding protein .of the resveratrol on the cell of MCF-7/ADM. Conclusion Resveratrol could significantly inhibit MCF-7/ADM cells growth and its mechanism may be due to the fact that it could induce the differentiation of MCF-7/ADM by cell cycle arrest via resveratrol activation which was used as inhibitor of Cdk2 and interfere in the cell mitosis through interaction with the proteins of cystoskeleton. Resveratrol is a new anticancer precursor which is less toxic and highly efficient.