Combined liposome-mediated cytosine deaminase gene therapy with radiation in killing rectal cancer cells anal xenografts in athymic mice
Combined liposome-mediated cytosine deaminase gene therapy with radiation in killing rectal cancer cells anal xenografts in athymic mice
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脂质体介导的胞嘧啶脱氨酶基因疗法与放射联合杀死无胸腺小鼠肛门异种移植物的直肠癌细胞
DOI：
10.1158/1078-0432.ccr-04-2077
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发表时间：
2005-05-01
影响因子：
11.5
通讯作者：
Zuo, F
中科院分区：
文献类型：
--
作者：
Li, SY;Yu, B;Zuo, F
目的：评价胞嘧啶脱氨酶（CD）自杀基因治疗联合放射治疗的抗肿瘤效果，探索局部复发直肠癌的治疗新策略。实验设计：以人直肠癌HR-8348细胞系为研究对象，评价质粒p EGFP-N1和PXJ41-CD转染的效果。细胞暴露于辐射，然后脂质体介导转染。细胞抑制实验采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑法。通过移植HR-8348癌细胞裸鼠，观察脂质体介导的CD自杀基因联合放射治疗的抗肿瘤效果。结果：辐射可提高脂质体介导的CD基因转染效率。在2、4、6和8 Gy的辐射下，脂质体介导的转染效率分别从21.3%增加到62.2%、78.0%、83.2%和87.8%。CD表达增强。肿瘤细胞抑制实验表明，脂质体介导的CD基因治疗与放射联合治疗具有更强的抗肿瘤作用。采用HR-8348异种肿瘤移植模型，观察异种肿瘤移植抑制作用。与对照组相比，CD/5-氟胞嘧啶联合放疗组、CD/5-氟胞嘧啶联合放疗组、CD/5-氟胞嘧啶联合放疗组肿瘤体积分别降低81.5%、48.5%、37.4%，肿瘤湿重分别降低80%、41.7%、37.7%。结论：脂质体介导的CD基因治疗联合放射治疗是一种安全有效的抗癌方法。其治疗局部复发性直肠癌的疗效可满足临床治疗。
Purpose: The aim of this study was to assess the antitumor efficacy of combination of cytosine deaminase (CD) suicide gene therapy with radiation and to grope for new therapeutic strategy for local recurrent rectal cancer.Experimental Design: HR-8348 cell line of human rectal cancer was used to assess efficiency of transfection with plasmid p EGFP-N1 and PXJ41-CD. The cells were exposed to radiation followed by liposome-mediated transfection. Cell inhibition assay was done with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Antitumor efficacy of combined liposome-mediated CD suicide gene therapy with radiation was determined by treatment of nude mice bearing HR-8348 cancer cell xenograft.Results: The efficiency of liposome-mediated CD gene transfection can be improved by radiation. With radiation at 2, 4, 6, and 8 Gy, the efficiency of liposome-mediated transfection increased from 21.3% to 62.2%,78.0%, 83.2%, and 87.8%, respectively. CD expression was enhanced as well. Cancer cell inhibition experiment showed that combined liposome-mediated CD gene therapy with radiation had much stronger antitumor effect. With HR-8348 tumor xenograft model, suppression of tumor xenograft was observed. Compared with control group, tumor volume was inhibited by 81.5%, 48.5%, and 37.4%, respectively, in the combined CD/5-fluorocytosine with radiation group, CD/5-fluorocytosine group, and radiation group and the wet weight of tumor was decreased by 80%, 41.7%, and 37.7%, respectively.Conclusion: These findings suggested that combination of liposome-mediated CD gene therapy with radiation is a safer and efficient anticancer method. Its therapeutic efficacy may meet clinical treatment on local recurrent rectal cancer.