摘要
目的探讨郭志强经验方紫草散对宫颈癌荷瘤裸鼠自噬的影响及作用机制。方法建立人宫颈癌Siha细胞荷瘤裸鼠模型,将30只成瘤裸鼠按随机数字表法分为模型组,顺铂组,紫草散高、中、低剂量组,每组各6只。模型组不干预,顺铂组腹腔内注射0.5 ml顺铂(5 mg/kg),1次/4 d,紫草散高、中、低剂量组分别在瘤体表面涂抹紫草散0.9248 mg/kg、0.4714 mg/kg、0.2357 mg/kg,1次/d,连续用药28 d。每天记录裸鼠重量及肿瘤体积,实验结束后处死裸鼠,取出完整肿瘤组织后称重并测量体积,将肿瘤组织切片并行HE染色,行移植瘤组织病理学观察,并采用免疫组化实验方法及蛋白免疫印迹法(Western blot)检测,分析荷瘤裸鼠瘤体信号通路Wnt抑制因子(Wnt inhibitory factor,Wnt)、β-连环蛋白(β-catenin)及自噬相关蛋白1轻链3(Microtuble associated protein light chain 3,LC3)、自噬特异性基因(Beclin 1)蛋白表达水平。结果与模型组比较,紫草散中、高剂量组及顺铂组在治疗第22、28天肿瘤体积减小(P<0.05),瘤重降低(P<0.05)。与模型组比较,紫草散中、高剂量组及顺铂组Wnt、β-catenin蛋白表达降低(P<0.05),LC3、Beclin1蛋白表达上升(P<0.05)。与顺铂组比较,紫草散各组Wnt、β-catenin蛋白表达均升高(P<0.05),LC3、Beclin1蛋白表达均降低(P<0.05)。与紫草散低剂量组比较,高剂量组Wnt、β-catenin降低(P<0.05),中、高剂量组LC3、Beclin1蛋白表达均升高(P<0.05)。结论紫草散可通过上调自噬相关蛋白LC3、Beclin1表达抑制肿瘤生长,其机制可能与Wnt/β-catenin信号通路有关。
Objective To investigate the effects and mechanisms of Guo Zhiqiang′s Zicao Powder on autophagy of cervical cancer cells in nude mice.Methods The human cervical cancer Siha cells tumor-bearing nude mouse model was built.Thirty nude mice with formed tumors were divided into the model group,cisplatin group,and high-,medium-and low-dose Zicao Powder groups by random number table method,with 6 mice in each group.No intervention was per⁃formed in the model group,mice in the cisplatin group were injected intraperitoneally with 0.5 mL cisplatin(5mg/kg)once every 4 days.The mice in the high-,medium-and low-dose groups were applied Zicao Powder of 0.9248 mg/kg,0.4714 mg/kg,and 0.2357 mg/kg respectively on the tumor body surface,once a day for 28 consecutive days.Body weight and tumor volume of nude mice were recorded daily and they were sacrificed after the experiment.The whole tumor tissue was removed to weigh and measure volume,and then it was sectioned,and performed HE staining.After that,the pathologi⁃cal changes in the transplanted tumor were observed,and they were detected using an immunohistochemical method and Western blotting to analyze the expression levels of Wnt inhibitory factor(Wnt),β-catenin protein,microtuble associated protein light chain 3(LC3),and Beclin 1 protein.Results Compared with the model group,the tumor volume and weight in the medium-and high-dose Zicao Powder groups and cisplatin group were decreased(P<0.05)on the 22nd and 28th treatment day,the Wnt andβ-catenin protein expression levels were decreased(P<0.05),and the LC3 and Beclin1 protein expression levels were increased(P<0.05).Compared with the cisplatin group,the Wnt andβ-catenin expres⁃sion levels were increased(P<0.05),and the LC3 and Beclin 1 protein expression levels were decreased(P<0.05)in each Zicao Powder group.Compared with the low-dose Zicao Powder group,Wnt andβ-catenin protein expression levels were decreased in the high-dose group(P<0.05),and LC3 and Beclin1 protein expression levels were increased in the me⁃dium-and high-dose groups(P<0.05).Conclusion Zicao Powder can inhibit tumor growth by upregulating autophagy-related proteins LC3 and Beclin1 protein,and the mechanisms may be related to the Wnt/β-catenin signaling pathway.
作者
温利娟
程玲
王浩
WEN Li-juan;CHENG Ling;WANG Hao(Shunyi Women′s&Children′s Hospital of Beijing Children′s Hospital,Beijing 101300;Wang Jing Hospital of CAC-MS,Beijing 100102)
出处
《世界中西医结合杂志》
2025年第1期112-117,共6页
World Journal of Integrated Traditional and Western Medicine
基金
北京市程玲中医妇幼名医传承工作室建设项目(2022-FYGZS-25)。