Bcl-XL反义寡核苷酸对裸鼠人食管癌移植瘤抑制作用的研究

Inhibitory Effects of Bcl-XL Antisense Oligodeoxynucleotide on Transplantation Tumor of Human Esophageal Carcinoma in Nude Mice

目的:探讨Bcl-XL反义寡核苷酸(ASODN)对裸鼠体内人食管癌移植瘤的抑制作用。方法:建立裸鼠体内人食管癌移植瘤动物模型,当移植瘤平均体积约为50mm3时,在裸鼠体内进行连续15d的Bcl-XLASODN治疗,观察人食管癌移植瘤的生长情况和组织形态学改变,应用RT-PCR和WesternBlot检测肿瘤组织中Bcl-XLmRNA和蛋白表达水平的改变以及凋亡的原位末端标记检测肿瘤的凋亡情况。结果:裸鼠体内人食管癌移植瘤的生长受到明显抑制,治疗后,对照组、无关序列寡核苷酸(N-ODN)组和ASODN组的移植瘤体积分别为(1062.8±599.7)mm3、(853.0±327.9)mm3和(267.7±152.3)mm3,ASODN组与对照组及N-ODN组比较,具有显著性差异(P<0.05)。同时,ASODN组的Bcl-XLmRNA及蛋白表达受到抑制,并且移植瘤组织中凋亡细胞显著增加(P<0.05)。结论:Bcl-XLASODN可有效抑制裸鼠体内人食管癌移植瘤的生长,为食管癌的基因治疗提供重要的理论依据。

Objective： To investigates the inhibitory effects of Bcl-XL antisense oligodeoxynucleotide on growth of human esophageal carcinoma in nude mice. Methods： The nude mice model carried esophageal cancer cell line EC9706 was constructed. When the mean volume of tumor reached 50mm^3, the nude mice were consecutively treated by ASODN for fifteen days. The tumor＇s volume was measured and the histopathological change of tumor observed using HE staining. The Bcl-XL gene and protein expressions was respectively detected, using RT-PCR and Western Blot. And apoptotic change was observed by in situ cell death detection. Results： Growth of human esophageal carcinoma was significantly inhibited in the ASODN therapy group. After treatment, the tumor volume in the control group, the non-sense oligonucleotide （N-ODN） group and the ASODN group was （1062.8±599.7） mm^3, （853.0±327.9） mm^3 and （267.7±152.3） mm^3, respectively. There was a significant difference in the ASODN group as compared with that in the control group and the N-ODN group （P〈0.05）. By the mean time, the expressions of Bcl-XL mRNA and protein were decreased, and the apoptosis of the tumor cells was increased significantly. Conclusion： Bcl-XL ASODN can effectively inhibit the growth of tumor in nude mice. It would offer an important theoretic foundation for the gene therapy of esophageal carcinoma.