GRK5对乳腺癌细胞生物学行为的影响

Effect of GRK5 on the biological behavior of breast cancer cells

目的探讨G蛋白偶联受体激酶5(GRK5)对乳腺癌细胞增殖、迁移、凋亡和紫杉醇化疗敏感性的影响,并初步探讨其发挥作用的可能机制。方法常规培养乳腺癌细胞系MDA-MB-435S,分为si-NC组和si-GRK5组,分别转染NC siRNA和GRK5 siRNA。采用Western blotting法检测GRK5 siRNA干扰效果;CCK-8实验检测GRK5对乳腺癌细胞增殖和紫杉醇化疗敏感性的影响;划痕实验检测GRK5对乳腺癌细胞迁移的影响;流式细胞仪检测GRK5对乳腺癌细胞凋亡的影响;Western blotting法检测GRK5对P53、MDM2和MMP2蛋白表达的影响。结果与si-NC组相比,si-GRK5组GRK5表达降低,细胞增殖和迁移能力降低,凋亡和紫杉醇化疗敏感性增加,P53蛋白表达增加,MDM2和MMP2蛋白表达降低(P均<0.05)。结论干扰GRK5的表达可抑制乳腺癌细胞增殖、迁移能力,促进细胞凋亡和对紫杉醇的敏感性,GRK5可能是治疗乳腺癌的潜在靶点。

Objective To investigate the effects of G protein-coupled receptor kinase 5(GRK5)on proliferation,migration,apoptosis,and chemosensitivity of paclitaxel in the breast cancer cells,and to explore its possible mechanism.Methods The breast cancer cell line MDA-MB-435S was routinely cultured,transfected with GRK5 siRNA,and then was divided into the si-NC and si-GRK5 groups.Western blotting was used to detect the interference effect of GRK5 siRNA;CCK-8 was used to detect the effect of GRK5 on breast cancer cell proliferation and paclitaxel chemotherapy sensitivity;Scratch assay was used to detect the effect of GRK5 on breast cancer cell migration;flow cytometry was used to detect the effect of GRK5 on apoptosis of breast cancer cells;Western blotting was used to detect the effects of GRK5 on the protein expression of P53,MDM2M,and MP2.Results Compared with the si-NC group,GRK5 expression decreased,the proliferation and migration abilities of the cells decreased,and the apoptosis and sensitivity of paclitaxel chemotherapy increased;the protein expression of P53 increased,and the protein expression of MDM2 and MMP7 decreased in the si-GRK5 group(all P<0.05).Conclusion Interfering with GRK5 expression can inhibit the proliferation and migration of breast cancer cells,promote apoptosis and sensitivity to paclitaxel;GRK5 may be a potential target for the treatment of breast cancer.