基于EGFR/STAT3途径探讨经络辨证逆针灸干预乳腺癌发生过程的作用机制

Effects and mechanism of meridian differentiation preventive acupuncture on the development process of breast cancer via the EGFR/STAT3 signaling pathway

目的:基于表皮生长因子受体(EGFR)/信号转导与转录激活因子(STAT3)增殖与凋亡途径研究经络辨证逆针灸在二甲基苯蒽(DMBA)诱导乳腺癌发生过程中的作用及机制。方法:选取8周龄清洁级雌性SD大鼠64只,随机分为对照组、模型组、他莫昔芬组和逆针灸组,每组16只。采用DMBA单次灌胃(100 mg/kg)诱导性乳腺癌模型。治疗周期结束后,统计肿瘤数量及质量,采用HE染色对大鼠乳腺组织进行组织病理学评估;免疫组化法和Western Blot法检测大鼠乳腺肿瘤组织中EGFR、STAT3的表达以及STAT3的磷酸化水平。结果:模型组大鼠平均体质量显著低于对照组(P<0.05)。他莫昔芬组及逆针灸组平均体质量略高于模型组大鼠平均体质量;与模型组比较,他莫昔芬组和逆针灸组两组大鼠的平均肿瘤数量及质量显著下降(P<0.01);DMBA诱导了(模型组)EGFR和STAT3磷酸化水平的高表达,与模型组比较,他莫昔芬组及逆针灸组EGFR蛋白表达水平和STAT3磷酸化水平显著降低(P<0.01)。结论:经络辨证逆针灸在DMBA诱导乳腺癌发生过程中的作用可能是通过调控增殖与凋亡相关的EGFR/STAT3通路而实现的。

Objective:To study the effects and mechanism of meridian identification preventive acupuncture on 7,12-dimethylbenz-(a)anthranene(DMBA)-induced mammary tumor model rats’epidermal growth factor receptor(EGFR)/signal transductor and activator of transcription(STAT3)signaling pathway proliferation and apoptosis.Methods:Sixty-four 8-week-old female SD rats were randomly assigned to four groups:control group,model group,Tamoxifen group,and preventive acupuncture group,16 rats in each group.The breast cancer model was induced with DMBA single gavage(100 mg/kg).End of treatment,tumor number and quality were counted,and HE staining was used to evaluate rat mammary tissues.Immunohistochemistry and Western Blot were used to detect EGFR,STAT3,and STAT3 phosphorylation.Results:Rats in the model group had considerably lower body weights than those in the control group(P<0.05).The Tamoxifen group and preventive acupuncture group had slightly higher body weights than the model group.The Tamoxifen group and preventive acupuncture group had significantly lower tumor numbers and masses compared to the model group(P<0.01);DMBA induced high phosphorylation expression.Compared with the model group,the protein expression level of EGFR and the phosphorylation level of STAT3 were significantly lower in the Tamoxifen group and the preventive acupuncture group(P<0.01).Conclusion:Meridian identification preventive acupuncture may be effective in preventing DMBA-induced breast cancer by regulating EGFR/STAT3 pathway-related proteins to balance cell proliferation and death.