注射维生素C治疗脑胶质瘤的实验研究

Experimental study on intravenously administered vitamin C in treatment of C6 rat glioma

目的探讨维生素C治疗脑胶质瘤的作用机制,为胶质瘤的临床治疗提供实验室依据。方法制作大鼠C6脑胶质瘤模型。荷瘤7d后将Wistar大鼠随机分为5组,每组10只,即对照组;维生素C低剂量组(2.0g/kg);维生素C中剂量组(4.0g/kg);维生素C高剂量组(8.0g/kg);5-Fu组(20mg/kg)。于用药结束后次日处死各组小鼠,计算肿瘤体积和抑瘤率;流式细胞术检测各组肿瘤组织细胞凋亡率;免疫组化法检测各组肿瘤组织Ki-67蛋白表达情况。结果维生素C可抑制大鼠肿瘤生长,且呈剂量依赖性,实验组肿瘤体积与对照组相比有显著差异(P<0.05),维生素C高剂量组与5-Fu组肿瘤体积比较无统计学差异(P>0.05)。维生素C可诱导大鼠肿瘤细胞凋亡,维生素C各组与对照组相比均有极显著性差异(P<0.01),维生素C高剂量组凋亡率高于5-Fu组(P<0.05)。免疫组化法检测肿瘤组织细胞Ki-67蛋白表达中,维生素C各组与对照组相比均有极显著性差异(P<0.01),维生素C高剂量组与5-Fu组细胞凋亡率比较无统计学差异(P>0.05)。结论维生素C在一定剂量范围内可抑制C6大鼠脑胶质瘤的生长,诱导肿瘤细胞发生凋亡是其机制之一;药理剂量的维生素C能降低C6大鼠脑胶质瘤细胞增殖活性,具有一定的抗肿瘤作用。

Objective To investigate the mechanisms of vitamin C on C6 rat glioma,and to provide experimental evidence for vitamin C on the therapy of glioma. Methods Fifty rats were injected with 1.0× 106 C6 cells into the right caudate nucleus area with stereotactic techniques. The rats were randomized into five groups, ten in each group. The control group received intraper- itoneal injection of normal saline, the rats in vitamin C groups received intraperitoneal injection of low--dose vitamin C（2.0g/kg）, middle--dose vitamin C（4. 0g/kg） and high--dose vitamin C （8.0g/kg）, 5--Fu group received intraperitoneal injection of 5--Fu（20mg/kg）. Fourteen days lat- er,all rats were killed, the tumor were taken, then the inhibitory rate of tumor growth could be calculated. At the same time,apoptotic rate of tumor tissue cells of every group was examined by FCM. The expression of Ki--67 protein of tumor tissue cells was analyzed by immunohistochem- istry. Results Vitamin C could inhibit the growth of rat tumors with a dose--dependent manner. There was statistically difference between the control group and every vitamin C treated group（P d0. 05）. There was no statistically significant difference between 5--Fu group and high--dose vi- tamin C group （P〉0. 05）. Vitamin C could induce apoptosis of rat tumor cells, there was statisti- cally significant difference between the control group and every vitamin C treated group （P〈0.01）. The apoptotic rate of 5--Fu group was lower than high--dose vitamin C group（P〈0.05）. The expressions of Ki--67 protein of tumor cells were analyzed by immunohistochemistry, there was statistically difference between the control group and every vitamin C treated group （P〈O. 01）,,and there was no statistically significant difference between 5--Fu group and high--dosevitamin C group （P）O. 05）. Conclusion Vitamin C could inhibit growth of C6 rat glioma in a dose--dependent manner within a certain concentration. Certain pharmacological doses of vitamin C could induce apoptosis and reduce the proliferation of C6 rat glioma cell.