KIAA1456抑制人卵巢癌裸鼠皮下移植瘤的生长

Inhibition of KIAA1456 on subcutaneous xenografts of human epithelial ovarian carcinoma in nude mice

摘要:

目的：探讨KIAA1456对人卵巢癌细胞株HO-8910PM裸鼠皮下移植瘤生长的影响。方法：将15只裸鼠随机分成3组：空白组（PM组），阴性对照组[PM（NC）组]，实验组[PM（KIAA1456）组]。利用人卵巢癌细胞株HO8910PM及本课题组前期通过慢病毒介导建立的阴性对照组细胞株HO8910PM（NC）和过表达KIAA1456的细胞株HO8910PM（KIAA1456）分别在空白组、阴性对照组、实验组建立裸鼠皮下移植瘤，待成瘤成功后，分别用PBS缓冲液和携带针对随机无关序列（NC）的慢病毒液Lentivirus-NC（作为阴性对照，LV-NC），携带KIAA1456病毒液Lentivirus-KIAA1456（LV-KIAA1456）每隔4 d进行一次瘤内定点注射治疗至28 d处死裸鼠，绘制肿瘤生长曲线并计算抑瘤率；采用实时荧光定量PCR和Western blot检测移植瘤组织中KI－AA1456的表达情况；免疫组化检测移植瘤中ki-67和PCNA的表达情况。结果：HO8910PM（KIAA1456）移植瘤组KIAA1456表达量明显高于阴性对照组和空白对照组（P=0.000）；28 d后处死裸鼠，HO8910PM（KIAA1456）组皮下移植瘤的体积明显小于阴性对照组和空白对照组（P=0.000），抑瘤效果明显；移植瘤组织中KIAA1456的表达上调，ki-67和PCNA表达明显下调。HO8910PM（KIAA1456）组移植瘤组织中ki-67和PCNA的表达明显低于阴性对照组和空白对照组，差异具有统计学意义（P=0.000）。结论：过表达KIAA1456基因对人上皮性卵巢癌细胞HO8910PM裸鼠皮下成瘤的生长具有抑制作用，有望成为卵巢癌基因治疗的新靶点。

Abstract:

Objective：To investigate the effect of KIAA1456 on the growth of subcutaneous xenografts of human epithelial ovarian cancer cell line HO-8910PM in nude mice. Methods：Fifteen SPF female BALB/c-nu nude mice were randomly divided into three groups：blank group（PM），negative control group[PM（NC）]，experimental group[PM（KIAA1456）]. The human ovarian cancer cell line HO8910PM，the negative control group HO8910PM（NC） and the cell line HO8910PM over expression KIAA1456[HO8910PM（KIAA1456）] were inoculated respectively into subcutaneous of each group to establish subcutaneous xenografts model in nude mice. After the tumor was successfully formed，the PBS buffer，venous fluid LV-NC and LV-KIAA1456 were respectively intratumoral injected in three groups for every four days. The nude mice were killed at the 28th day. The tumor growth curve was drawn and the tumor inhibition rate was calculated. The expression level of KIAA1456 mRNA and protein in xenografts was detected by Real-time fluorogenic quantitative PCR and Western blot. The expression of ki-67 and PCNA was detected by immunohistochemistry. Results： The expression of KIAA1456 in the HO8910PM（KIAA1456） xenografts group was significantly higher than that in the negative con－trol group and blank control group（P=0.000）. The volume of subcutaneous xenografts in HO8910PM（KIAA1456） group was signifi－cantly smaller than that in the negative control group and blank control group（P=0.000）. The expression of ki-67 and PCNA in the HO8910PM（KIAA1456） group was significantly lower than that in the negative control group and the blank control group，with statis－tically significant differences（P=0.000）. Conclusion：Overex－pression of KIAA1456 inhibits the growth of human epithelial ovarian cancer cell HO8910PM in nude mice subcutaneously，which is expected to be a new target for oncogene therapy.