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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 investigate the effect of postoperative breast cancer on HER2-mediated p38 MAPK, PI3K-Akt signaling pathway and its effect on HER2-overexpressing breast cancer cell motility and adhesion, and to evaluate the effect of postoperative breast cancer on the recurrence and metastasis of HER2 overexpressing breast cancer mechanism. Methods Twenty-three-week-old spontaneous breast cancer mice bearing HER2 / neu tumors of similar tumor size were selected for primary tumor resection. The patients were randomly divided into control group, TCM group (CRF group), western medicine group Beads monoclonal antibody group), combined group (postoperative breast cancer + trastuzumab group), intervention for 4 months. The tumor recurrence rate, tumor suppression rate and lung metastasis inhibition rate were evaluated. Western blot was used to detect the expression of Total-Akt, p-Akt, p38, p38 in HER2-related signal pathways in the recurrent tumor tissues of mice in each group after intervention p38 and the expression of E-cadherin and Vimentin, a marker of epithelial-mesenchymal transition, related to cell motility and adhesion. Results ① There was no significant difference in tumor recurrence rate among the three groups (P> 0.05). The average tumor volume at the end of treatment was 11.11 cm3 in the control group and 5.56 cm3 in the traditional Chinese medicine group, with a significant difference between the two groups (P = 0.037). In the control group, the average number of lung metastases was 16, that of the traditional Chinese medicine group was 10, Group lung metastasis inhibition rate was 37.85%, but there was no significant difference within the group (P> 0.05). ②The expressions of p-p38 and p-Akt in Chinese medicine group, Western medicine group and combined group were significantly lower than those in control group (P <0.05); E-cadherin expression in control group and combination group was almost not expressed; E-cadherin expression in traditional Chinese medicine group and western medicine group Significantly increased (P <0.05). Vimentin expression levels in recurrent tumor tissues of each group were similar. Conclusion Breast cancer after operation can inhibit the growth of recurrent breast tumor in HER-2 / neu transgenic mice, block HER2-mediated p38 MAPK and PI3K-Akt signaling pathways, inhibit tumor cell proliferation and promote tumor cell apoptosis , Exert antitumor effect. The expression of E-cadherin can be up-regulated after breast cancer surgery, which may play an anti-metastatic role by increasing the cohesion of cells and maintaining the integrity of breast epithelial cells.