TAT-OSBP-MKK6（E）抑制卵巢癌裸鼠腹腔移植瘤恶性生物学行为的研究∗

摘要

Objective To investigate the effects of TAT⁃OSBP⁃MKK6( E) on the tumor growth, invasion and metastasis of o⁃varian cancer xenograft in nude mice in vivo. Methods Eighteen female nude mice were randomly assigned to three groups:treatment group[TAT⁃OSBP⁃MKK6(E)],negative group[TAT⁃OSBP⁃MKK6(E)+SB202190]and control group(saline only).The cell lines were inoculated respectively into abdominal cavity of each group to establish intraperitoneal xenograft model of human ovarian cancer. Ab⁃dominal circumference were recorded every two days,the nude mice were sacrificed four weeks after inoculation. The ascitic volume, dissemination position number, disseminated tumor number, tumor weight and tumor growth inhibition rate were recorded. Histopatho⁃logical characteristics for xenograft tissues were observed by hematoxylin and eosin( HE) staining. Cell apoptosis in tumor tissues was observed by TUNEL method and apoptotic index ( AI) was calculated. The expressions of vascular endothelial growth factor ( VEGF) and p38 in xenograft tissues were detected by immunohistochemical staining or Western blotting. Results Compared with the negative group and control group, the abdominal circumference growth in treatment group was delay with statistical significance (P<0�05).The treatment group had decreased in ascitic volume( P<0�05) ,dissemination position number ( P<0�05) , disseminated tumor number( P<0�05) and tumor weight(P<0�05), with tumor growth inhibition rate of 70�99%. the AI in the treatment group was(20�44±1�20)%, higher than (4�94±0�24)% of negative group and (4�00±0�79)% of control group, with statistical significance(P<0�05).The ex⁃ pression of VEGF in the treatment group (21�2%)was decreased compared to negative group(81�4%) and control group(85�7%), with statistical significance(P<0�05). The relative expression of p38 was significantly increased in the treatment group (0�40±0�01) compared to negative group (0�22±0�01) and control group(0�20±0�01), with statistical significance(P<0�05).Conclusion TAT⁃OSBP⁃MKK6( E) can significantly suppress the tumor growth, invasion and metastasis of human ovarian cancer in nude mice xenograft.%目的：探讨TAT⁃OSBP⁃MKK6（ E）对人卵巢癌裸鼠腹腔移植瘤生长、侵袭及转移等恶性生物学行为的影响。方法18只裸鼠随机分为实验组[TAT⁃OSBP⁃MKK6（E）]、阴性对照组[TAT⁃OSBP⁃MKK6（E）＋SB202190]和空白对照组（生理盐水），每组6只，细胞接种法建立人卵巢癌腹腔移植瘤模型，每2天测量腹围。4周后解剖裸鼠，观察裸鼠成瘤情况，测定腹水量，统计肿瘤播散器官数及瘤结节数，称量瘤体重量并计算抑瘤率。采用HE染色分析移植瘤的病理形态学特点；采用TUNEL法检测移植瘤组织的细胞凋亡指数（ AI）；免疫组化SP法检测各组移植瘤组织中血管内皮生长因子（ VEGF）的表达；Western blotting检测各组移植瘤组织中p38蛋白表达。结果与阴性对照组和空白对照组比较，实验组裸鼠腹围增长明显滞后（ P＜0�05），腹水量明显减少（ P＜0�05），肿瘤播散器官数、瘤结节数及瘤体重量均明显减少（ P均＜0�05），抑瘤率达70�99％。实验组的AI为（20�44±1�20）％，显著高于阴性对照组的（4�94±0�24）％和空白对照组的（4�00±0�79）％，差异均有统计学意义（ P＜0�05）；实验组VEGF蛋白的阳性表达率为21�2％，显著低于阴性对照组的81�4％和空白对照组的85�7％，差异均有统计学意义（P＜0�05）；实验组p38蛋白的相对表达量为0�40±0�01，显著高于阴性对照组的0�22±0�01和空白对照组的0�20±0�01，差异均有统计学意义（P＜0�05）。结论 TAT⁃OSBP⁃MKK6（E）能显著抑制人卵巢癌裸鼠腹腔移植瘤的生长、侵袭及转移。