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肺岩宁方联合吉非替尼抑制肺癌裸鼠移植瘤细胞H1975生长及其作用机制

Mechanism of Feiyanning Combined with Gefitinib inhibiting growth of Lung Adenocarcinoma Cell H1975 in Xenograft Nude Mice Models

  • 摘要: 目的 观察肺岩宁方联合吉非替尼对肺腺癌裸鼠移植瘤细胞H1975生长的影响并探讨其可能的作用机制。方法 成功建立H1975细胞裸鼠皮下移植瘤模型后,随机分为模型组、吉非替尼组、肺岩宁方组及联合用药组,每组10只,分别用相应药物干预4周,检测肿瘤体积、瘤重、体重等,绘制肿瘤生长曲线,计算肿瘤抑制率;应用TNUEL法检测移植瘤细胞凋亡;应用Western blot法检测EGFR-PI3K/AKT信号通路相关蛋白表达。结果 各组的抑瘤率模型组为0,吉非替尼组21.91%,肺岩宁方组25.11%,联合用药组53.28%;各组移植瘤组织中肿瘤细胞的凋亡率分别为模型组(15.11±1.6)%,吉非替尼组(26.64±0.69)%,肺岩宁方组(28.88±1.61)%,联合用药组(55.06±2.39)%。联合用药组与模型组及单用吉非替尼、肺岩宁方相比差异有统计学意义(P<0.01)。Western blot结果显示肺岩宁方联合吉非替尼在不影响EGFR、AKT、mTOR总蛋白表达的情况下,可显著下调p-EGFR、p-AKT、p-mTOR水平。结论 肺岩宁方联合吉非替尼可显著抑制H1975肺癌裸鼠移植瘤的生长,促进肿瘤细胞凋亡,其作用机制可能与阻断EGFR-PI3K/AKT信号通路有关。

     

    Abstract: Objective To investigate the potential mechanisms of Feiyanning combined with Gefitinib inhibiting growth of lung adenocarcinoma cell H1975. Methods H1975 human lung adenocarcinoma cells were implanted subcutaneously in the left armpits of male athymic nude mice to establish transplantation tumor models of human lung cancer. Forty models were randomly and evenly divided into four groups, Control group, Feiyanning group (F), Gefi tinib (G) group and F+G group, and treated with corresponding drugs for 4 weeks. Tumor volume, tumor weight and body weight were measured to draw up tumor growth curves and calculated the tumor weight inhibition rates. The aoptotic rates were measured by TUNEL stain method, and the expressions of EGFR-PI3K/AKT pathway related proteins were detected by Western blot. Results The tumor weight inhibition rates were 0, 21.91%, 25.11%, 53.28% of groups of Control, Gefitinib, Feiyanning and F+G respectively. The apoptotic rate of F+G was(55.06±2.39)%, which was increased significantly compared with Control group(15.11±1.6)%, Gefitinib group (26.64±0.69)% and Feiyanning group(28.88±1.61)% (P<0.01). The result of Western blot showed that the expressions of p-EGFR, p-AKT and p-mTOR were decreased signifi cantly in F + G group. Conclusion Feiyanning combined with Gefi tinib may be blockade EGFR-PI3K/AKT pathway to inhibit the tumor growth and induce apoptosis of lung adenocarcinoma cell H1975 in xenograft nude mice models.

     

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