hTR-siRNA腺病毒对裸鼠人宫颈癌移植瘤的治疗作用
herapy for Human Cervical Cancer Xenografts in Nude Mice Mediated by siRNA-hTR Adenovirus
目的 探讨hTR-siRNA腺病毒对裸鼠人宫颈癌移植瘤的治疗作用及其机制。方法 将HeLa细胞注射到裸鼠的右腋皮下建立肿瘤模型,27 d后将荷瘤裸鼠随机分为4组,采用瘤体内多点注射方式,分别向各组荷瘤鼠注射0.1 ml的DMEM、Ad-NT-siRNA (1010pfu/ml)、Ad-hTR-siRNA (1010pfu/ml)或顺铂(1.20mg/ml), 以后每隔3 d注射一次, 连续15 d。观察注射腺病毒后移植瘤的体积变化、毒副作用。治疗结束后间隔7 d处死动物,剥离出肿瘤组织称重。切取瘤组织做HE染色观察肿瘤组织的形态学变化,并做TUNEL染色测定组织的凋亡指数。结果 将HeLa细胞移植到裸鼠皮下,成瘤率为100%。与Ad-NT-siRNA处理组相比,用Ad-hTR-siRNA处理裸鼠动物模型,可以使移植瘤的体积和重量分别降低45.48%和34.68%,HE染色显示大量的瘤细胞可能经历了坏死、凋亡,TUNEL分析显示凋亡细胞量约11.8%;但是Ad-hTR-siRNA的抗肿瘤作用不及顺铂。结论 hTR-siRNA腺病毒能够明显抑制裸鼠人宫颈癌移植瘤的生长,其抗肿瘤机制与诱导肿瘤细胞凋亡、坏死有关。因此,该腺病毒在肿瘤基因治疗方面具有潜在的应用价值。
im To study the effect of the hTR-siRNA adenovirus on anti-tumor in vivo and its mechanism. Methods HeLa cells were subcutaneous inoculated into the right armpit of BALB/c nu/nu mice to establish the model of human cervical cancer. After successful implantation, the mice were randomized into four groups. The mice were intratumorally injected with 0.1ml of serum-free DMEM alone, or Ad-hTR-siRNA (1010 pfu/ml), or Ad-NT-siRNA (1010 pfu/ml), or cisplatin(1.20 mg/ml) as positive control. These different treatments were given once every 3 days for 15 consecutive days. After the last injection, mice were observed for 7 days continuously and sacrificed at the end. Tumors were excised, weighed, sectioned and assessed for morphology by HE and for apoptosis by the TUNEL assay. Results Tumors-implanted were established successfully by 100% with HeLa cells. As compared with Ad-NT-siRNA-treated mice, Ad-hTR-siRNA could slow down tumor growth, decrease tumor volume (45.48%) and tumor weight (34.68%) and push forward the apoptosis and necrosis of tumor cells. The TUNEL positive cells were about 11.8%. But the anti-tumor activity of Ad-hTR-siRNA didn’t catch on cisplatin’s. Conclusion It is supposed that the hTR-siRNA adenovirus could suppress cervical cancer-xenografted growth in vivo and induce tumor cell apoptosis or necrosis. All of these indicated the prospect of applying this siRNA expressing recombinant adenovirus system in cancer gene therapy.
李小玉、张思源、刘豫蓉、李明远、李婉宜、李燕、肖丽英
肿瘤学基础医学
宫颈癌 腺病毒 RNA干扰 hTR基因
ervical cancer Adenovirus RNA interference Human telomerase RNA
李小玉,张思源,刘豫蓉,李明远,李婉宜,李燕,肖丽英.hTR-siRNA腺病毒对裸鼠人宫颈癌移植瘤的治疗作用[EB/OL].(2007-10-29)[2025-08-19].http://www.paper.edu.cn/releasepaper/content/200710-509.点此复制
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