摘要
目的探讨乳癌术后方对HER2介导的p38 MAPK、PI3K-Akt信号通路及其对HER2过表达乳腺癌细胞运动和黏附能力的影响,评价乳癌术后方抗HER2过表达乳腺癌复发转移的作用机制。方法选取30周龄左右发瘤相当的HER2/neu转基因自发乳腺癌小鼠,行原发肿瘤切除术,术后随机分为对照组、中药组(乳癌术后方组)、西药组(曲妥珠单抗组)、联合组(乳癌术后方+曲妥珠单抗组),干预4个月。评价肿瘤的复发率、瘤积抑制率及肺转移抑制率;并采用Western blot法检测干预结束后各组小鼠复发肿瘤组织中HER2相关信号通路中Total-Akt、p-Akt、p38、p-p38的表达及与细胞运动和黏附相关的基质蛋白细胞间黏附分子(E-cadherin)、上皮间质转化标记物波形蛋白(Vimentin)的表达情况。结果①各组小鼠肿瘤复发率差异无统计学意义(P>0.05)。对照组治疗结束时平均瘤积为11.11 cm3,中药组为5.56 cm3,组间差异有统计学意义(P=0.037);对照组平均肺转移结节数为16个,中药组为10个,中药组肺转移抑制率达37.85%,但组内差异无统计学意义(P>0.05)。②中药组、西药组、联合组p-p38及p-Akt表达含量较对照组明显下调(P<0.05);对照组与联合组E-cadherin几乎不表达,中药组与西药组E-cadherin表达显著增加(P<0.05)。各组复发肿瘤组织中Vimentin表达水平相似。结论乳癌术后方能够抑制HER-2/neu转基因小鼠术后乳腺复发肿瘤瘤积的增长,阻断HER2介导的p38 MAPK及PI3K-Akt信号通路,抑制肿瘤细胞增殖,促进肿瘤细胞凋亡,发挥抗肿瘤作用;乳癌术后方能够上调细胞间黏附分子E-cadherin的表达,其可能通过增加细胞间的黏聚力,维持乳腺上皮细胞的完整性,发挥抗复发转移作用。
Objective To explore the influence of ＂Ru＇ai Shuhou Recipe＂（RSR） on p38 MAPK,PI3K-Akt signal pathway and its impact on breast cancer cell motility and adhesion mediated by HER2/neu oncogene over-expression,and to evaluate the mechanism of RSR in the prevention of HER2 over-expression in breast cancer recurrence and metastasis.Methods Selected HER2/neu transgenic spontaneous breast tumor model mice aged around 30 weeks with similar tumor size for primary tumor resection.After surgery randomly divided them into control group,traditional Chinese medicine group（RSR group）,western medicine group（Trastuzumab group）,and the combination group（RSR and Trastuzumab group） and treated with corresponding medicine for 4 month.The recurrence rate of tumor,inhibition rate of tumor volume and inhibition rate of lung metastasis were evaluated;the expression of Total-Akt,p-Akt,p38,p-p38 in the recurrent mice tumor tissue and expression of E-cadherin and Vimentin in each group were detected by Western blot assay.Results ① After treatment,no statistical significance was found in tumor recurrence rate in each group（P0.05）.The average recurrent tumor volume was 11.11 cm3 in control group and 5.56 cm3 in RSR group,with significant differences between the two groups（P=0.037）;the average lung metastatic nodules was 16 in control group and 10 in RSR group,and the inhibition rate of lung metastasis of RSR group was 37.85%,without statistical significance（P0.05）.② The expression of p-p38 and p-Akt in RSR group,Herceptin group and combination group were decreased compared with the control group（P0.05）,E-cadherin barely expressed in control group and combination group,while the expression of E-cadherin in RSR group and Herceptin group were increased significantly（P0.05）.The expression of Vimentin in each group showed no significant difference.Conclusion ＂Ru＇ai Shuhou Recipe＂ can inhibit recurrent tumor volume in transgenic mice after operation,block the HER2-mediated p38 MAPK and PI3K-Akt sig
出处
《上海中医药杂志》
2013年第6期89-92,共4页
Shanghai Journal of Traditional Chinese Medicine
基金
上海市自然科学基金项目(09ZR1432500)
上海市卫生局基金项目(2009Y087)
