论文部分内容阅读
目的:探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)抑制剂吉非替尼对平滑肌细胞(smooth muscle cells,VSMC)和内皮细胞(ndothelial cells,EC)增殖的影响,以及对EGFR和Akt蛋白表达及磷酸化的影响。方法:将大鼠VSMC及EC置于含0.01~10μmol·L的吉非替尼的培养基中培养24~72 h,以MTT法测定细胞增殖的抑制率。Western blot检测EGFR及磷酸化EGFR(p-EGFR)、Akt及磷酸化Akt(p-Akt)蛋白水平。结果:MTT结果显示,吉非替尼抑制VSMC增殖呈时间和浓度依赖性,而吉非替尼对EC增殖的抑制作用明显低于紫杉醇;Western blot结果显示VSMC中EGFR(1.07±0.13)表达与EC(0.58±0.05)相比明显增多(P<0.01),而吉非替尼可明显抑制VSMC中EGFR及Akt蛋白的磷酸化。结论:类似紫于杉醇,吉非替尼可抑制VSMC增殖,而对EC的细胞毒性作用明显低于紫杉醇,其机制可能是通过抑制EGFR及Akt蛋白磷酸化来实现的。
Objective: To investigate the effect of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, on the proliferation of smooth muscle cells (VSMC) and endothelial cells (ndothelial cells) Protein Expression and Phosphorylation. Methods: Rat VSMCs and ECs were incubated in gefitinib with 0.01 ~ 10μmol·L for 24-72 h. The inhibitory rates of cell proliferation were determined by MTT assay. Western blot was used to detect the protein levels of EGFR, phosphorylated EGFR (p-EGFR), Akt and phosphorylated Akt (p-Akt). Results: MTT showed that gefitinib inhibited VSMC proliferation in a time and concentration-dependent manner, while gefitinib inhibited the proliferation of EC significantly lower than paclitaxel; Western blot results showed that the expression of EGFR (1.07 ± 0.13) and EC (0.58 ± 0.05) (P <0.01), while gefitinib significantly inhibited the phosphorylation of EGFR and Akt in VSMC. CONCLUSION: Similar to paclitaxel, gefitinib inhibits the proliferation of VSMCs, while the cytotoxic effect on EC is much lower than that of paclitaxel. The possible mechanism is that gefitinib may inhibit EGFR and Akt protein phosphorylation.