Li Shiyong, Yu Bo, An Ping, Chen Gang, Lu Wenping, Cai Huiyun, Guo Wenhua, Zuo Fuyi
Department of General Surgery, General Hospital of Beijing Military Command, Beijing, China.
Clin Cancer Res. 2005 May 1;11(9):3574-8. doi: 10.1158/1078-0432.CCR-04-2077.
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.
HR-8348 cell line of human rectal cancer was used to assess efficiency of transfection with plasmid pEGFP-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.
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.
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.
本研究旨在评估胞嘧啶脱氨酶（CD）自杀基因疗法联合放疗的抗肿瘤疗效，并探索局部复发性直肠癌的新治疗策略。
用人直肠癌HR-8348细胞系评估质粒pEGFP-N1和PXJ41-CD的转染效率。细胞先接受放疗，然后进行脂质体介导的转染。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法进行细胞抑制试验。通过对携带HR-8348癌细胞异种移植瘤的裸鼠进行治疗，确定脂质体介导的CD自杀基因疗法联合放疗的抗肿瘤疗效。
放疗可提高脂质体介导的CD基因转染效率。在2、4、6和8 Gy的放疗剂量下，脂质体介导的转染效率分别从21.3%提高到62.2%、78.0%、83.2%和87.8%。CD表达也增强。癌细胞抑制实验表明，脂质体介导的CD基因疗法联合放疗具有更强的抗肿瘤作用。在HR-8348肿瘤异种移植模型中，观察到肿瘤异种移植受到抑制。与对照组相比，CD/5-氟胞嘧啶联合放疗组、CD/5-氟胞嘧啶组和放疗组的肿瘤体积分别被抑制了81.5%、48.5%和37.4%，肿瘤湿重分别下降了80%、41.7%和37.7%。
这些发现表明，脂质体介导的CD基因疗法联合放疗是一种安全有效的抗癌方法。其治疗效果可能满足局部复发性直肠癌的临床治疗需求。
