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目的:观察肠胃清对结肠癌肝转移裸小鼠生存期、肿瘤生长及对肿瘤组织铜转运相关蛋白表达的影响,探讨肠胃清对结直肠癌化疗增效的作用机制。方法:BALB/C裸小鼠,采用HCT116细胞建立裸小鼠结肠癌肝转移模型,随机分为模型组,肠胃清组、化疗组、肠胃清联合化疗组(联合组),每组20只,肠胃清组ig给予相应药物,ip生理盐水,化疗组ip奥沙利铂(L-OHP),5-氟尿嘧啶(5-FU),ig给予生理盐水,联合组ig给予肠胃清,ip L-OHP,5-FU,模型组ig和ip生理盐水,连续给药3周。观察肠胃清对荷瘤小鼠生存期及肿瘤生长的影响;利用免疫组化观察肿瘤组织人铜离子转运蛋白1(h CTR1),铜转运蛋白α链(ATP7A)和P型铜转运ATP酶(ATP7B),多药耐药相关蛋白2(MRP2),谷胱甘肽S-转移酶-π(GST-π)蛋白表达的影响;采用TUNEL法观察移植瘤组织细胞凋亡率。结果:与模型组比较,肠胃清组、化疗组、联合组抑瘤率分别为45.33%,70.51%,72.07%,以联合组明显(P<0.01);肠胃清组、化疗组、联合组裸小鼠生存时间均长于模型组(P<0.05);肠胃清组、联合组肿瘤组织中h CTR1的表达阳性率均高于模型组和化疗组(P<0.05);肠胃清组、联合组ATP7A,ATP7B和GST-π的表达阳性率均低于模型组和化疗组(P<0.05);肠胃清组、联合组的MRP2表达阳性率低于模型组(P<0.05);联合组凋亡指数高于化疗组和模型组(P<0.01)。结论:肠胃清能上调肝转移瘤组织h CTR1的表达,下调ATP7A和ATP7B蛋白表达,降低GST-π和MRP2的表达,并有增加肿瘤组织内铂药物含量的趋势,同时能诱导细胞凋亡,增加肿瘤细胞凋亡率,从而提高化疗敏感性。
OBJECTIVE: To observe the effect of Gengweiqing on the survival, tumor growth and the expression of copper transporter related proteins in tumor tissues of hepatocellular carcinoma in nude mice with colon cancer and to explore the mechanism of the effect of gingweiqing on the chemosensitivity of colorectal cancer. Methods: BALB / C nude mice were randomly divided into model group, Changweizheng group, chemotherapy group and combined group of gastrointestinal tract and chemotherapy group (combination group) with HCT116 cells. Twenty mice in each group, The rats in the group of stomach and intestine were given ig with the corresponding drugs, ip saline, chemotherapy group ip oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) , 5-FU, model group ig and ip saline, continuous administration for 3 weeks. To observe the effect of Gweiweiqing on the survival and tumor growth of tumor-bearing mice. Immunohistochemistry was used to observe the expression of hTRT, ATP7A and P-copper transport ATPase ATP7B), multidrug resistance-associated protein 2 (MRP2), and glutathione S-transferase-π (GST-π) protein expression were detected by flow cytometry. TUNEL method was used to observe the apoptotic rate of transplanted tumor cells. Results: Compared with the model group, the inhibitory rates of JGG, chemotherapy and combination group were 45.33%, 70.51% and 72.07%, respectively, which were significantly lower in the combined group (P <0.01) The survival time of mice in model group was longer than that in model group (P <0.05). The positive expression rate of hTRT1 in model group and chemotherapy group was significantly higher than those in model group and chemotherapy group (P <0.05) (P <0.05). The positive rate of MRP2 expression in JGG and the combined group was lower than that in the model group (P <0.05). The positive rate of ATP7B and GST-π in the combined group was lower than that in the model group and the chemotherapy group Higher than chemotherapy group and model group (P <0.01). Conclusion: Changweiqing can up-regulate the expression of hTRT1, down-regulate the expression of ATP7A and ATP7B, decrease the expression of GST-π and MRP2, and increase the content of platinum in tumor tissue, meanwhile induce apoptosis, Increase the rate of tumor cell apoptosis, thereby enhancing the sensitivity of chemotherapy.