扶正抗癌方对Lewis肺癌荷瘤小鼠肺癌基因Bcl-2、抑癌基因Bax及血管内皮生长因子、表皮生长因子受体、金属蛋白酶表达的影响
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摘要
目的:观察扶正抗癌方对小鼠Lewis肺癌抗转移机制的影响。方法:选取C57BL/6小鼠50只,雌雄各半,每只小鼠腋窝下接种肿瘤细胞0. 2 m L造模,24 h后,完全随机分为对照组、顺铂组、扶正抗癌方低、中、高剂量组,每组10只。分别给药21 d后取出完整肿瘤组织称重计算抑瘤率,同时用实时荧光定量PCR检测Lewis肺癌组织Bcl-2和Bax mRNA的表达,免疫组化检测Lewis肺癌组织基质金属蛋白酶-9(MMP-9)蛋白的表达,用蛋白质印迹法(WB法)检测Lewis肺癌组织血管内皮生长因子(VEGF)、表皮生长因子受体(EGFR)的表达。结果:与模型组小鼠比较,扶正抗癌方药可以呈剂量依赖性抑制Lewis肺癌荷瘤小鼠肿瘤生长,显著升高Lewis肺癌组织中Bax mRNA表达,降低Bcl-2 mRNA、MMP-9蛋白表达,与模型组比较,差异有统计学意义(P <0. 05),其中高剂量组在升高Lewis肺癌组织中Bax mRNA表达、降低Bcl-2 mRNA表达方面与顺铂组比较,差异有统计学意义(P <0. 05)。同时模型组Lewis肺癌组织中VEGF、EGFR表达显著升高,扶正抗癌方药可显著降低Lewis肺癌组织中VEGF、EGFR表达,与模型组比较,差异有统计学意义(P <0. 05),与顺铂组比较,无统计学意义(P> 0. 05)。结论:虽然扶正抗癌方总体上较顺铂作用偏弱,但依然能有效抑制肺癌细胞增殖,抑制肺癌细胞Bcl-2基因的表达,激活Bax的高表达,下调肺癌细胞中VEGF、EGFR、MMP的表达。
Objective: To observe Fuzheng Kangai Decoction on the anti-transfer mechanism of Lewis lung cancer in mice. Methods: A total of 50 C57 BL/6 mice,half male and half female,were selected,and each mouse was inoculated with 0. 2 m L of tumor cells under the armpit for 24 hours,and then were randomly divided into control group,DDP group,Fuzheng Kangai Decoction low,medium and high dose group,with 10 mice in each group. They were respectively administrated for 21 days,and the complete tumor tissue was taken out for weighing inhibitory rate calculation. The expression of Bcl-2 and Bax mRNA in Lewis lung cancer tissues were detected by Real-time fluorescent quantitative polymerase chain reaction (PCR) detection. The expression of MMP-9 protein in Lewis lung cancer tissues was detected by immunohistochemistry. And the expression of vascular endothelial growth factor (VEGF),epidermal growth factor receptor (EGFR) in Lewis lung cancer tissues was detected by method of western blot (WB).Results: Compared with the model group,Fuzheng Kangai Decoction could inhibit the tumor growth of Lewis lung cancer-bearing mice in a dose-dependent manner,and significantly increase the expressions of Bax mRNA in Lewis lung cancer tissues,and decrease the expression of Bcl-2 mRNA and MMP-9 protein. There were significant differences compared with the model group (P <0. 01). The expressions of VEGF,EGFR in Lewis lung cancer tissues was significantly increased in the model group,and Fuzheng Kangai Decoction could significantly reduce the expressions of VEGF,EGFR in Lewis lung cancer tissues. There was a significant difference compared with the model group (P < 0. 01,0. 05). Conclusion: Fuzheng Kangai Decoction can inhibit lung cancer cell proliferation,inhibit the expression of Bcl-2 gene in lung cancer cells,activate the high expression of Bax and down-regulate the expression of VEGF,EGFR and MMP in lung cancer cells.
Objective: To observe Fuzheng Kangai Decoction on the anti-transfer mechanism of Lewis lung cancer in mice. Methods: A total of 50 C57 BL/6 mice,half male and half female,were selected,and each mouse was inoculated with 0. 2 m L of tumor cells under the armpit for 24 hours,and then were randomly divided into control group,DDP group,Fuzheng Kangai Decoction low,medium and high dose group,with 10 mice in each group. They were respectively administrated for 21 days,and the complete tumor tissue was taken out for weighing inhibitory rate calculation. The expression of Bcl-2 and Bax mRNA in Lewis lung cancer tissues were detected by Real-time fluorescent quantitative polymerase chain reaction (PCR) detection. The expression of MMP-9 protein in Lewis lung cancer tissues was detected by immunohistochemistry. And the expression of vascular endothelial growth factor (VEGF),epidermal growth factor receptor (EGFR) in Lewis lung cancer tissues was detected by method of western blot (WB).Results: Compared with the model group,Fuzheng Kangai Decoction could inhibit the tumor growth of Lewis lung cancer-bearing mice in a dose-dependent manner,and significantly increase the expressions of Bax mRNA in Lewis lung cancer tissues,and decrease the expression of Bcl-2 mRNA and MMP-9 protein. There were significant differences compared with the model group (P <0. 01). The expressions of VEGF,EGFR in Lewis lung cancer tissues was significantly increased in the model group,and Fuzheng Kangai Decoction could significantly reduce the expressions of VEGF,EGFR in Lewis lung cancer tissues. There was a significant difference compared with the model group (P < 0. 01,0. 05). Conclusion: Fuzheng Kangai Decoction can inhibit lung cancer cell proliferation,inhibit the expression of Bcl-2 gene in lung cancer cells,activate the high expression of Bax and down-regulate the expression of VEGF,EGFR and MMP in lung cancer cells.
引文
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[10]王堃,何娜萍,吴琼,等.血管内皮生长因子在肺癌中的临床应用价值[J].检验医学,2016,31(9):765-769.
[11]孟谊,杨杨,樊祥山,等.VEGF、EGFR的表达与非小细胞肺癌生物学行为的相关性[J].现代肿瘤医学,2015,23(5):633-636.
[12]曹文荣,闫文修,王雪利,等.非小细胞肺癌组织中VEGF和Bax的表达及意义[J].重庆医学,2016,45(3):307-309.
[13]黄信刚,周淮英.表皮生长因子受体在肺癌、肺结核的表达[J].中国现代医学杂志,2005,15(10):1509-1511.
[14]霍婷婷,贾金虎.EGFR基因检测在非小细胞肺癌诊疗应用中的新进展[J].癌症进展,2016,14(6):507-509,513.
[15]赵军,刘叙仪,张青云,等.晚期非小细胞肺癌患者外周血VEGF和bFGF及MMP-9水平与预后的关系[J].中华肿瘤杂志,2005,27(11):676-679.
[2]Siegel RL,Miller KD,Jemal A.Cancer statistics,2015[J].CA Cancer J Clin,2015,65(1):5-29.
[3]石远凯,孙燕,于金明,等.中国晚期原发性肺癌诊治专家共识(2016年版)[J].中国肺癌杂志,2016,19(1):1-15.
[4]陈文杰,李高峰.非小细胞肺癌的分子靶向治疗研究进展[J].现代肿瘤医学,2017,25(12):1994-1996.
[5]成娅婷,田成旺,任涛,等.中药治疗非小细胞肺癌的临床应用及作用机制研究进展[J].药物评价研究,2016,39(2):289-295.
[6]陈嘉璐,李湧健.中医药治疗晚期非小细胞肺癌临床观察[J].中医学报,2017,32(5):711-714.
[7]钟永泷,林辉,李柏钧,等.非小细胞肺癌组织CCR9和Survivin及Bcl-2表达相关性研究[J].中华肿瘤防治杂志,2013,20(16):1232-1235.
[8]李军,王晓敏,宋张骏,等.非小细胞肺癌中Ki-67和BCL-2表达的临床意义及预后价值[J].临床与实验病理学杂志,2012,28(8):921-924.
[9]马家宝,朱文,周清华.bag-1、bcl-2和bax在非小细胞肺癌中的表达和意义及其与化疗多药耐药相关性的研究[J].中国肺癌杂志,2009,12(10):1089-1094.
[10]王堃,何娜萍,吴琼,等.血管内皮生长因子在肺癌中的临床应用价值[J].检验医学,2016,31(9):765-769.
[11]孟谊,杨杨,樊祥山,等.VEGF、EGFR的表达与非小细胞肺癌生物学行为的相关性[J].现代肿瘤医学,2015,23(5):633-636.
[12]曹文荣,闫文修,王雪利,等.非小细胞肺癌组织中VEGF和Bax的表达及意义[J].重庆医学,2016,45(3):307-309.
[13]黄信刚,周淮英.表皮生长因子受体在肺癌、肺结核的表达[J].中国现代医学杂志,2005,15(10):1509-1511.
[14]霍婷婷,贾金虎.EGFR基因检测在非小细胞肺癌诊疗应用中的新进展[J].癌症进展,2016,14(6):507-509,513.
[15]赵军,刘叙仪,张青云,等.晚期非小细胞肺癌患者外周血VEGF和bFGF及MMP-9水平与预后的关系[J].中华肿瘤杂志,2005,27(11):676-679.