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目的 :观察HSV1 tk/GCV基因治疗系统与 5 FU序贯应用 ,对卵巢上皮癌SKOV3细胞的体内杀伤效应。方法 :建立裸鼠卵巢癌皮下移植瘤模型 ,免疫组化检测移植瘤组织中表皮生长因子受体 (EGFR)的表达 ;于瘤周分别注射GE7 β gal、GE7 HSV1 tk复合物 ,用X gal及RT PCR检测两种基因的表达 ;取 2 4只荷瘤裸鼠随机分成空白对照组、5 FU组、GE7 HSV1 tk/GCV组及GE7 HSV1 tk/GCV/5 FU组进行实验 ,观察肿瘤体积及重量的变化 ,计算各组抑瘤率。结果 :移植瘤中有较高的EGFR表达 ,β gal基因及HSV1 tk基因经瘤周注射导入移植瘤后均有不同程度的表达 ,5 FU组、GE7 HSV1 tk/GCV组及GE7 HSV1 tk/GCV/5 FU组抑瘤率分别为 14 .6 %、39.4 %和 6 0 .5 % (P <0 .0 5 )。结论 :HSV1 tk/GCV和 5 FU序贯治疗能有效地抑制肿瘤生长 ,并能有效地抑制单纯使用HSV1 tk/GCV系统治疗后的远期反跳作用 ,提高卵巢癌基因治疗的远期疗效。
OBJECTIVE: To observe the in vivo killing effect of HSV1 tk / GCV gene therapy system and sequential application of 5 FU on human ovarian epithelial carcinoma SKOV3 cells. Methods: The subcutaneous xenograft model of ovarian cancer in nude mice was established. The expression of epidermal growth factor receptor (EGFR) was detected by immunohistochemical staining. GE7 β gal and GE7 HSV1 tk complexes were injected into the peritumoral region, RT-PCR was used to detect the expression of both genes. Twenty-four nude mice bearing tumor were randomly divided into blank control group, 5 FU group, GE7 HSV1 tk / GCV group and GE7 HSV1 tk / GCV / 5 FU group. Weight changes, calculate the inhibition rate of each group. Results: The expression of EGFR was higher in the xenografts and the expressions of β gal gene and HSV1 tk gene were all significantly different after transplanted into the tumor by peritumor injection. The expression of tk / GCV in 5 FU group, GE7 HSV1 tk / GCV group and GE7 HSV1 tk / GCV group / 5 FU inhibition rate was 14.6%, 39.4% and 6.5% (P <0. 05). Conclusions: The sequential therapy of HSV1 tk / GCV and 5 FU can effectively inhibit tumor growth, and can effectively inhibit the long-term reflex action after HSV1 tk / GCV treatment and improve the long-term efficacy of ovarian cancer gene therapy.