多药耐药基因转染后加大化疗剂量以杀灭早期肝癌细胞的作用研究

目的 探讨恶性肿瘤MDRI基因治疗以后,加大化疗剂量,提高早期肝癌细胞的杀伤效果。方法 用培养的H22腹水型肝癌细胞注入balb/c 小鼠制成肿瘤模型,同种骨髓造血细胞经浓缩病毒上清法转染MDRI基因后,程序性移植入预先照射亚致死剂量60Co-γ射线的荷瘤小鼠,再经大剂量化疗。实验分为空白对照组（X=0.2mg/kg）、阴性对照（X=5 mg/kg）和阿霉素（X=5mg/kg最大剂量）组、（2X=10mg/kg）组、（4X=20mg/kg）组及逐渐加量（1-2-4-6-8-8X）组3个剂量组,分别在化疗3d后观察小鼠白细胞的变化情况,测定小鼠瘤体的大小、计算抑瘤率。结果 从第1周开始实验组白细胞明显高于空白对照组、阴性对照组（P<0.01）,阴性对照组白细胞前3周明显高于空白对照组,从第4周无明显差异（P>0.05）,实验组之间从第2周开始有明显差异（P<0.01）。瘤重从第1周开始实验组白细胞明显高于空白对照组、阴性对照组（P<0.01）,实验组之间从第1周开始有明显差异（P<0.01）,空白对照组、阴性对照组之间无明显差异（P>0.05）。剂量较大其抑瘤率较高。结论 MDRI基因治疗保护骨髓的情况下,大剂量化疗可以杀灭恶性肿瘤细胞,抑制肿瘤的迅速生长。

Protective effect of the bone by MDR1 gene transfering into the hematopoietic cells in chemotherapy of hepatocarcinoma marrow

Objective To investigate the effect of the bone during the chemotherapy of earlier period hepatocar-cinoma balb/c mice. Methods Cultivated H22 hepatocarcinoma cell was injected into the balb/c mouse to make the animal model. MDR1 gene was transferred into hematopoietic cells of murine bone marrow by retrovirus vecter and transplanted into the balb/c mouse with hepatocarcinoma exposed to Co - 7 ray in advance. The experiment animals were divided into 5 groups, blank control, negative control, 5 mg/kg group, 10 mg/kg group, gradually raise dose group. WBC were investigated 3 days after undergoing high - dose chemotherapy. The weight of tumor was measured and the suppression rate was calculated. Results WBC of different dose experiment groups were significantly higher than those of negative control group and blank control group ( P < 0.01) since the first week, in the first three weeks counting of WBC of negative control group was higher than that of blank control group ( P < 0.01) , but there was no significant difference ( P >0.05) in the last three weeks, from the second week there were obviously difference ( P <0.01) from the first weeks. Suppression rate of high dose group was higher than that of lower dose group. Conclusions MDR1 gene transfer can protect the bone, so can increase the chemotherapy dose to kill tumor cell.