乳癌术后方对HER2阳性乳腺癌复发转移小鼠NF-κB表达的影响

Effect of Ru′ai Shuhou Recipe on the Expression of NF-κB in the Recurrence and Metastasis of Breast Cancer Mice with Positive HER2

目的比较乳癌术后方原方与精简方抗HER2阳性乳腺癌复发转移小鼠的疗效,探讨其对转基因小鼠复发转移过程中NF-κB表达的影响。方法选取30周龄左右HER2/neu转基因自发乳腺癌小鼠,行体表原发肿瘤切除术,术后随机分为对照组(纯净水0.2mL/d灌胃)、原方组(乳癌术后方0.2mL/d灌胃)、精简方组(乳癌术后方精简方0.2mL/d灌胃)及西药组(曲妥珠单抗1mg/kg腹腔注射,每周2次),每组15只,连续干预4个月,评价小鼠体表肿瘤再发率、再发肿瘤瘤积、生存率及肺转移发生情况,Western Blot及免疫组化法检测小鼠再发肿瘤组织中NF-κB蛋白表达情况。结果各组小鼠治疗结束时体表肿瘤再发率及生存率差异无统计学意义(P>0.05)。与对照组比较,原方组及精简方组体表再发肿瘤瘤积缩小(P<0.05),精简方组、西药组p-NF-κB/NF-κB下调(P<0.01),西药组NF-κB表达降低(P=0.013)。精简方组肺转移结节数最少,肺转移抑制率达81.9%,但组间比较差异无统计学意义(P>0.05)。结论乳癌术后方精简方与原方疗效相当,其可能通过抑制NF-κB的活化,减少其在胞核内的定位发挥抗HER2阳性乳腺癌复发转移作用。

Objective To compare the anti-tumor recurrent and metastatic efficacy between Ru＇ ai Shuhou Recipe（RSR） and simplified RSR, and to explore the effects of RSR on the expression of NF- κB in the recurrence and metastasis of HER2 positive transgenic breast tumor model mice. Methods We selected HER2/neu transgenic spontaneous breast tumor model mice, aged around 30 weeks for pri- mary tumor resection. After surgery ,they were randomly divided into the control group（ administered with purified drinking water 0.2 mL/d by gastrogavage） ,RSR group（administered with RSR 0.2 mL/d by gas- trogavage）, simplified RSR group （administered with simplified RSR 0.2 mL/d by gastrogavage） and Western medicine group（administered with Herceptin 1 mg by intraperitoneal injection, twice a week）, 15 mice in each group. After treatment for 4 months, the recurrence rate of tumor, tumor volume, overall survival and condition of lung metastasis were evaluated. We used Western Blot and immunohistochemi- cal method to detect the expression of NF-κB in the recurrent mice tumor tissue. Results After treat- ment, no statistical significance was found in tumor recurrence rate and overall survival in each group （P 〉0.05）. Compared with the control group, the average recurrent tumor volume in RSR group and sim- plified RSR group were smaller （P 〈0.05）, p-NF-κB/NF-κB in the simplified RSR group and Western med- icine group were down-regulated （P 〈0.01 ）, the expression of NF-κB in Western medicine group were de- creased （P =0. 013）. The number of lung metastasis nodules of simplified RSR group was least and its in-hibition rate of lung metastasis was 81.98%, although no statistical significance was found among the groups （P 〉0.05）. Conclusion The simplified RSR was equivalent to the original prescription, it might play a role in anti-tumor recurrent and metastatic efficacy by inhibiting the activation of NF-κB and reduc- ing its localization Jn the nucleus.