硫代磷酸反义寡核苷酸对裸鼠原位移植人胃癌生长和肝转移的影响研究

Effects of ASODN on Growth and Liver Metastasis of Orthotopic Transplanted Human Gastric Carcinoma in Nude Mice

目的:探讨作用于端粒酶催化亚基的硫代磷酸反义寡核苷酸(ASODN)对裸鼠人胃癌生长和肝转移的影响,为治疗胃癌肝转移提供依据。方法:建立裸鼠人胃癌原位移植肝脏高转移模型,传15代后分别用生理盐水,5-氟尿嘧啶(5-Fu)、ASODN单用及合用进行干预,之后检测各组肿瘤生长及免疫组化指标。结果:与生理盐水组比较,5-Fu、ASODN单药组和合用组原位肿瘤重量明显降低,体积明显缩小,肝转移率、增殖细胞核心抗原及端粒酶阳性率均降低,尤以合用组作用更明显,3组抑瘤率分别为37.52%、58.76%、98.51%。结论:ASODN可抑制裸鼠原发胃癌的生长及肝转移,尤其与5-Fu合用能明显增强其效果。

OBJECTIVE： To study the effects of telomerase catalytic subunit - acted ASODN on the growth and liver metastasis of orthotopic transplanted human gastric cancer in nude mice acting so as to provide basis for the treatment of liver metastasis of gastric carcinoma. METHODS： High liver metastasis of orthotopic human gastric cancer implantation model was established in nude mice, which were treated with normal saline, 5-Fu and ASODN alone and in combination after culture for 15 generations, then growth of tumor and immunohistochemical index were detected. RESULTS： As compared with mice treated with normal saline, those mice treated with 5- Fu and ASODN either alone or in combination had significant reductions in weight and size of tumor, rate of liver metastasis, and the expressions of PCNA and telomerase, with the combination group showing significant higher efficacy. The inhibition rates of tumor in 3 groups were 37.52%, 58.76 and 98.51% respectively. CONCLUSION： ASODN can inhibit the growth and liver metastasis of primary gastric cancer in nude mice, with its efficacy markedly enhanced when used concomitantly with 5- Fu.