黄芪、莪术单药及配伍通过影响上皮间质转化抑制Lewis荷瘤小鼠肺转移的研究
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摘要
目的通过观察黄芪、莪术及其配伍应用对Lewis荷瘤小鼠肺转移灶数目及肿瘤上皮间质转化的影响,研究其基于上皮间质转化机制抑制肿瘤转移的作用,并分析黄芪、莪术配伍应用的意义。方法将50只C57 Lewis荷瘤小鼠模型随机分为模型组、顺铂组、黄芪单药组、莪术单药组及黄芪-莪术配伍组,接种后次日开始连续15 d,分别给予相应药物干预,处死后解剖取出肺脏,解剖显微镜下观察双肺表面超过2 mm结节数目;剥离腋下种植瘤体,EnVision法检测肿瘤组织中E-cad、MMP-2、MMP-9表达。结果顺铂组和配伍组肺转移结节数量少于模型组(均P<0.05),单药组肺转移灶数量虽均少于模型组但差异无统计学意义(P>0.05);各中药组均不及顺铂组(P<0.05),配伍组少于黄芪、莪术单药组,但差异无统计学意义(P>0.05)。E-cad表达,与模型组相比,顺铂组、配伍组升高(均P<0.05),单药组与模型组比差异均无统计学意义(P>0.05);各中药组低于顺铂组(均P<0.05),配伍组高于莪术组(P<0.05),与黄芪组差异无统计学意义(P>0.05)。MMP-2表达,各组差异无统计学意义(P>0.05)。MMP-9表达,顺铂组、配伍组、莪术单药组低于模型组(均P<0.05),黄芪组与模型组比较差异无统计学意义(P>0.05);各中药组高于顺铂组(均P<0.05),配伍组低于黄芪组(P<0.05),与莪术单药组接近,差异无统计学意义(P>0.05)。结论黄芪-莪术配伍抑制肿瘤转移的效果优于单用黄芪、莪术,其作用机制为提高E-cad蛋白表达、降低MMP-9表达;黄芪、莪术配伍使用在提高E-cad表达上优于单用黄芪、莪术,在降低MMP-9表达上与莪术相近、优于单用黄芪。
To observe the effects of Astragalus membranaceus,Curcuma and its compatibility on the number of lung metastases and tumor epithelial-mesenchymal transition in Lewis tumor-bearing mice in order to study the role of epithelial-mesenchymal transition mechanism in inhibiting tumor metastasis, and analyze the application significance of Radix Astragali and Rhizoma Zedoariae compatibility.Methods Fifty mice with C57 Lewis tumors were randomly divided into model group,Cisplatin group,Huangqi single drug group,Ezhu single drug group and compatibility group.The mice were given drug intervention accordingly for 15 consecutive days after inoculation.The lungs were dissected for observation,and the number of nodules as big as more than 2 mm over the surface of the lungs was observed under a dissecting microscope; the tumor was removed from the underarms and the EnVision method was used to detect E-cad,MMP-2,and MMP-9 in the tumor tissues.Results The number of pulmonary metastatic nodules in the cisplatin group and the compatibility group was lower than that in the model group(P<0.05).The number of lung metastases in two monotherapy groups was less than that of the model group but there was no statistical difference;that in each Chinese medicine group was inferior to that in the cisplatin group(P<0.05),that in the compatibility group was less than that in the Huangqi and Ezhu group,but the difference did not show statistical significance.E-cad expression was higher in the cisplatin group and the compatibility group than in the model group(P<0.05).There was no significant difference between the two monotherapy groups and the model group;that in the Chinese medicine group was lower than that in the cisplatin group(P<0.05),that in the compatibility group was higher than that in the Ezhu group(P<0.05),compared with that in the Huangqi single drug group,there was not statistically significant.The expression of MMP-2 was not statistically significant in each group(P>0.05).The expression of MMP-9 was lower in the cisplatin group,the compatibility group,and the Ezhu group than that in the model group(P<0.05).There was no significant difference between the Huangqi group and the model group;that in each group was higher than that in the cisplatin group(P<0.05),that in the compatibility group was lower than that in the Huangqi single drug group,while similar to that in the Ezhu single drug group and there was no statistical difference between the compatibility group and the Huangqi monotherapy group(P<0.05).Conclusion The effect of Huangqi-Ezhu compatibility in inhibiting tumor metastasis is better than that of Huangqi and Ezhu used singly.The mechanism may be related to the increase of E-cad protein expression and the decrease of MMP-9 expression.The combination of Huangqi and Ezhu is superior to use them singly in enhancing E-cad expression,but is similar with Ezhu and better than Huangqi in decreasing the expression of MMP-9.
To observe the effects of Astragalus membranaceus,Curcuma and its compatibility on the number of lung metastases and tumor epithelial-mesenchymal transition in Lewis tumor-bearing mice in order to study the role of epithelial-mesenchymal transition mechanism in inhibiting tumor metastasis, and analyze the application significance of Radix Astragali and Rhizoma Zedoariae compatibility.Methods Fifty mice with C57 Lewis tumors were randomly divided into model group,Cisplatin group,Huangqi single drug group,Ezhu single drug group and compatibility group.The mice were given drug intervention accordingly for 15 consecutive days after inoculation.The lungs were dissected for observation,and the number of nodules as big as more than 2 mm over the surface of the lungs was observed under a dissecting microscope; the tumor was removed from the underarms and the EnVision method was used to detect E-cad,MMP-2,and MMP-9 in the tumor tissues.Results The number of pulmonary metastatic nodules in the cisplatin group and the compatibility group was lower than that in the model group(P<0.05).The number of lung metastases in two monotherapy groups was less than that of the model group but there was no statistical difference;that in each Chinese medicine group was inferior to that in the cisplatin group(P<0.05),that in the compatibility group was less than that in the Huangqi and Ezhu group,but the difference did not show statistical significance.E-cad expression was higher in the cisplatin group and the compatibility group than in the model group(P<0.05).There was no significant difference between the two monotherapy groups and the model group;that in the Chinese medicine group was lower than that in the cisplatin group(P<0.05),that in the compatibility group was higher than that in the Ezhu group(P<0.05),compared with that in the Huangqi single drug group,there was not statistically significant.The expression of MMP-2 was not statistically significant in each group(P>0.05).The expression of MMP-9 was lower in the cisplatin group,the compatibility group,and the Ezhu group than that in the model group(P<0.05).There was no significant difference between the Huangqi group and the model group;that in each group was higher than that in the cisplatin group(P<0.05),that in the compatibility group was lower than that in the Huangqi single drug group,while similar to that in the Ezhu single drug group and there was no statistical difference between the compatibility group and the Huangqi monotherapy group(P<0.05).Conclusion The effect of Huangqi-Ezhu compatibility in inhibiting tumor metastasis is better than that of Huangqi and Ezhu used singly.The mechanism may be related to the increase of E-cad protein expression and the decrease of MMP-9 expression.The combination of Huangqi and Ezhu is superior to use them singly in enhancing E-cad expression,but is similar with Ezhu and better than Huangqi in decreasing the expression of MMP-9.
引文
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[7] 于明薇,孙桂芝,张培彤,等.不同类型活血药及其与益气药配伍对小鼠Lewis肺癌生长转移的干预作用[J].北京中医药,2011,30(11):859-862.
[8] 陈慧彬,陈超,滕鸣健,等.扶正散结汤拆方配伍中药对Lewis肺癌转移及血管生成影响的研究[J].中华中医药学刊,2014,32(12):3025-3027.
[9] 骆殊,邵佳,沈洪,等.黄芪莪术配伍抑制MKN -45裸鼠人原位胃癌模型肿瘤生长、转移及COX -2表达的增效研究[J].时珍国医国药,2012,23(5):1164-1165.
[10] 尹刚,唐德才,戴建国,等.黄芪、莪术配伍对人卵巢癌HO-8910原位移植瘤组织中MMP2和VEGF表达的影响[J].南京中医药大学学报,2014,30(1):53-56.
[2] 陈奇.中药药理研究方法学[M]北京:人民卫生出版社,2011:1262.
[3] Thiery JP.Epithelial-mesenchymal transitions in tumour progression[J].Nature Reviews Cancer,2002,2(6):442-454.
[4] Katsuno Y,Lamouille S,Derynek R.TGF-β signaling and epithelial-mesenchymal transition in cancer progression[J].Curr Opin Oncol,2013,25(1):76-84.
[5] Lin YS,Tsai PH,Kandaswami CC,et al.Effects of dietary flavonoids,luteolin,and quercetin on the reversal of epithelial–mesenchymal transition in A431 epidermal cancer cells[J].Cancer Sci,2011,102(10):1829-1839.
[6] 郭鹏.社区癌症高危人群与中医体质相关性分析[J].北京中医药,2016,35(12):1169-1171.
[7] 于明薇,孙桂芝,张培彤,等.不同类型活血药及其与益气药配伍对小鼠Lewis肺癌生长转移的干预作用[J].北京中医药,2011,30(11):859-862.
[8] 陈慧彬,陈超,滕鸣健,等.扶正散结汤拆方配伍中药对Lewis肺癌转移及血管生成影响的研究[J].中华中医药学刊,2014,32(12):3025-3027.
[9] 骆殊,邵佳,沈洪,等.黄芪莪术配伍抑制MKN -45裸鼠人原位胃癌模型肿瘤生长、转移及COX -2表达的增效研究[J].时珍国医国药,2012,23(5):1164-1165.
[10] 尹刚,唐德才,戴建国,等.黄芪、莪术配伍对人卵巢癌HO-8910原位移植瘤组织中MMP2和VEGF表达的影响[J].南京中医药大学学报,2014,30(1):53-56.