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目的探讨受体酪氨酸激酶抑制剂Gefitinib在体内外对激素非依赖前列腺癌(HIPC)的抑制作用及其效应机制。方法不同浓度的Gefitinib处理HIPC细胞株PC-3后24～120h,MTT法检测细胞生长抑制率,Westernblot检测细胞表皮生长因子受体(EGFR)、蛋白激酶B(Akt)、丝裂原活化蛋白激酶(MAPK)和蛋白激酶C(PKC)蛋白的表达水平。建立PC-3细胞裸鼠移植瘤,观察Gefitinib体内的肿瘤抑制率。结果Gefitinib抑制PC-3细胞生长呈现时间-浓度依赖性,最佳抑制浓度为5ng/mL,最佳抑制时间为72h,细胞生长抑制率稳定在50%～60%。与对照组比较,经Gefitinib处理后PC-3细胞中EGFR、Akt蛋白水平分别降低了70.44%和59.01%,而MAPK及PKC蛋白分别仅降低34.83%和33.40%。裸鼠实验结果表明,Gefitinib可显著抑制HIPC肿瘤的生长,抑制率高达53.95%,常规病理HE染色提示大片灶状癌细胞坏死。结论Gefitinib可在体内外显著抑制HIPC的生长,其机制可能为通过降低癌细胞EGFR和胞内蛋白Akt的表达水平来发挥作用。
Objective To investigate the inhibitory effect of Gefitinib, a receptor tyrosine kinase inhibitor, on hormone-independent prostate cancer (HIPC) in vitro and in vivo and its mechanism. Methods The cell growth inhibition rate was determined by MTT assay after treatment with different concentrations of Gefitinib on HIPC cell line PC-3. The expressions of EGFR, Akt, mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) protein expression levels. The establishment of PC-3 cell xenografts in nude mice and the observation of the tumor inhibition rate in Gefitinib. Results Gefitinib inhibited the growth of PC-3 cells in a time-concentration-dependent manner. The optimal concentration of Gefitinib was 5ng / mL. The optimal inhibitory time was 72h. The growth inhibition rate of Gefitinib was stable at 50% -60%. Compared with the control group, the protein levels of EGFR and Akt decreased by 70.44% and 59.01% in the PC-3 cells treated with Gefitinib, while the MAPK and PKC proteins decreased only by 34.83% and 33.40%, respectively. Nude mice experimental results show that, Gefitinib can significantly inhibit the growth of HIPC tumors, the inhibition rate as high as 53.95%, conventional pathological HE staining prompted a large number of focal necrosis of cancer cells. Conclusion Gefitinib can significantly inhibit the growth of HIPC both in vitro and in vivo. The mechanism may be that Gefitinib can reduce the expression of EGFR and Akt in cancer cells.