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目的探讨皂角刺总黄酮体内外对小鼠肺癌的防治作用及其机制。方法用不同质量浓度皂角刺总黄酮处理体外培养的小鼠Lewis肺癌细胞和L929胚肺成纤维细胞48 h,MTT法检测细胞增殖与黏附,划痕标记染料示踪技术观察细胞连接通讯的功能。将小鼠分成模型组、槲皮素(100 mg/kg)阳性对照组、皂角刺总黄酮高和低剂量(100、30 mg/kg)组,每周2次、连续5周ip乌拉坦制备小鼠肺癌模型,ip乌拉坦1次后开始给药,每天1次,连续给药10周,另设对照组。免疫组化法检测肺肿瘤部位间隙连接蛋白43(Cx43,)的表达。建立小鼠Lewis肺癌皮下移植模型和肺转移模型,实验设模型组、阿霉素(5 mg/kg)阳性对照组、皂角刺总黄酮高和低剂量组(100、30 mg/kg),模型建立后次日给药,连续给药3周,观察荷瘤小鼠存活时间。结果皂角刺总黄酮可剂量相关性抑制体外培养的Lewis肺癌细胞增殖;降低Lewis肺癌细胞黏附,并以剂量相关方式促进Lewis肺癌细胞间连接通讯,但对L929胚肺成纤维细胞黏附无影响;对乌拉坦诱导小鼠肺癌有预防作用,增强Cx43的免疫组化染色强度;对Lewis肺癌皮下肿瘤及实验性肺转移均具有剂量相关性抑制作用,能延长荷瘤小鼠的存活时间。结论皂角刺总黄酮能增强细胞连接通讯,选择性预防和治疗肺癌,是潜在抗肿瘤药物。
Objective To investigate the preventive and therapeutic effects and the mechanisms of total flavonoids of Radix Glabra on mouse lung cancer in vitro and in vivo. Methods The Lewis lung carcinoma cells and L929 embryonic lung fibroblasts cultured in vitro were treated with different concentrations of total flavonoids of Gleditsia sinensis for 48 h. The cell proliferation and adhesion were detected by MTT assay. The function of cell junctional communication . The mice were divided into model group, quercetin (100 mg / kg) positive control group, high and low dose (100, 30 mg / kg) Preparation of mouse lung cancer model, ip urethane once after the start of administration, 1 day, continuous administration of 10 weeks, the other a control group. Immunohistochemistry was used to detect the expression of connexin 43 (Cx43) in lung tumor. The mice model of lung cancer subcutaneous transplantation and lung metastasis were established. The model group, the positive control group of doxorubicin (5 mg / kg), the high and low dose of total flavonoids (100, 30 mg / kg) The model was administered the next day after administration, continuous administration for 3 weeks to observe tumor-bearing mice survival time. Results The total flavonoids of S. japonicus could dose-dependently inhibit the proliferation of Lewis lung cancer cells in vitro, reduce the adhesion of Lewis lung cancer cells and promote the connection of Lewis lung cancer cells in a dose-dependent manner, but had no effect on the adhesion of L929 embryonic lung fibroblasts. It could prevent the lung cancer of mice induced by urethane and enhance the intensity of Cx43 immunohistochemical staining. It could inhibit the growth of Lewis lung carcinoma in a dose-dependent manner and prolong the survival time of tumor-bearing mice. Conclusion The total flavonoids of Gleditsia sinensis can enhance the cellular connection and communication, and selectively prevent and treat lung cancer. It is a potential anticancer drug.