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目的:建立荷瘤小鼠模型,探讨川楝素对肝癌的抑瘤作用及其机制。方法:建立H22肝癌移植瘤小鼠模型,随机分为0.9%氯化钠溶液对照组、环磷酰胺(cyclophosphamide,CTX)组(20mg/kg)、川楝素低剂量组(0.173mg/kg)和川楝素高剂量组(0.690mg/kg)共4组。各组药物处理后,测量小鼠体内肿瘤大小,观察肿瘤的生长曲线;剥瘤后称重,计算小鼠的肿瘤抑制率;行肿瘤组织病理形态学及HE染色观察,透射电子显微镜观察其超微结构改变;同时,观察川楝素对荷瘤小鼠心、肝、脾、肾、胸腺及睾丸组织的影响;免疫组织化学法检测肿瘤组织内Bcl-2、Bax和Fas蛋白的表达。结果:川楝素可显著抑制小鼠体内肿瘤的生长,川楝素低剂量组(0.173mg/kg)和高剂量组(0.690mg/kg)的抑瘤率分别为66.23%和87.01%(P<0.05);透射电子显微镜观察可见肿瘤组织超微结构中出现凋亡小体;HE染色显示小鼠心、肝、脾、肾及睾丸脏器形态正常,而胸腺组织中可见胸腺小叶的数量及面积减少甚至消失;免疫组织化学检测证实,小鼠肿瘤组织内Bcl-2蛋白表达下调,Bax和Fas蛋白表达上调(P<0.05)。结论:川楝素能够明显抑制小鼠移植瘤的生长,此作用可能与抑制肿瘤细胞增殖及促进肿瘤细胞凋亡有关。
Objective: To establish a tumor-bearing mouse model and explore the antitumor effect of toosendanin on hepatocellular carcinoma and its mechanism. Methods: A mouse model of H22 hepatocellular carcinoma was established and randomly divided into 0.9% sodium chloride solution control group, cyclophosphamide (CTX) group (20mg / kg), toosendanin low dose group (0.173mg / kg) And toosendanin high dose group (0.690mg / kg) a total of 4 groups. After treatment, the tumor size in mice was measured and the growth curve of the tumor was observed. The tumor growth inhibition rate was calculated after tumor stripping. The tumor histopathology and HE staining were observed. Transmission electron microscopy Meanwhile, we observed the effect of toosendanin on the heart, liver, spleen, kidney, thymus and testis in tumor-bearing mice and the expression of Bcl-2, Bax and Fas protein in tumor tissue by immunohistochemistry. Results: Toosendanin could significantly inhibit tumor growth in mice, and the inhibitory rates of toosendanin low dose group (0.173mg / kg) and high dose group (0.690mg / kg) were 66.23% and 87.01%, respectively <0.05). Apoptotic bodies were observed in the ultrastructure of the tumor tissue by transmission electron microscopy. HE staining showed that the morphology of heart, liver, spleen, kidney and testis in mice was normal, while the number of thymus lobules in thymus and The area decreased or even disappeared. Immunohistochemistry confirmed that the expression of Bcl-2 protein and Bax and Fas proteins were up-regulated in tumor tissues of mice (P <0.05). Conclusion: Toosendanin can significantly inhibit the growth of transplanted tumor in mice, which may be related to the inhibition of tumor cell proliferation and the promotion of tumor cell apoptosis.