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阿西替尼联合5-FU对移植人肠癌细胞的裸鼠的治疗作用

Therapeutic effect of axitinib and 5-FU in nude mice bearing human colon cancer xenograft

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【作者】 赵佳招婷谢锋伟何本夫

【Author】 ZHAO Jia1,ZHAO Ting1,XIE Fengwei1,HE Benfu2 1Devision of Surgery,Emergency Center,Affiliated Hospital of Guangdong Medical College,Zhanjiang 524001,China;2Department of Oncology,421 Hospital of PLA,Guangzhou 510318,China

【机构】 广东医学院附属医院急救中心外科解放军第421医院肿瘤科

【摘要】 目的探讨阿西替尼联合5-FU对肠癌LoVo细胞裸鼠移植瘤的抑制作用及其毒性作用。方法肠癌LoVo细胞移植瘤裸鼠随机分为5组:空白对照组、溶剂对照组、阿西替尼组、5-FU组和联合用药组,分别给予处理。观察各组裸鼠肿瘤大体形态,并测定裸鼠体质量、肿瘤大小及计算瘤质量、完全缓解(CR)、部分缓解(PR)、T(2治疗后肿瘤增长至治疗前瘤体积2倍所需的时间)和肿瘤生长延迟时间(TGD),记录动物死亡率。结果联合用药组疗效优于阿西替尼及5-FU单药组。治疗后第30天联合用药组瘤质量小于对照组及阿西替尼和5-FU单药组(P<0.01)。联合用药组T(229.05 d)长于阿西替尼(19.31 d)和5-FU组(21.22 d)。联合用药组的TGD达16.73 d,较阿西替尼单药组和5-FU单药组的8.53 d和9.72 d,明显延长。除了空白对照组没有裸鼠死亡之外,其余4组均有1只死亡,死亡率未超过20%。此外,各组裸鼠的体质量下降也均未超过20%。阿西替尼组及联合组中各有1例获得部分缓解(PR)。阿西替尼组及联合用药组的瘤组织ABCG2蛋白水平较对照组表达显著下降(P<0.05),而5-FU组的ABCG2表达水平则较对照组无显著差异(P>0.05)。结论在人肠癌LoVo细胞裸鼠移植瘤模型中,阿西替尼和5-FU单药均能抑制肿瘤生长,两者联合使用显示出更强的抗肿瘤作用。两药剂量范围内的联合具有较佳的耐受性和安全性。

【Abstract】 Objective To study the inhibitory effect and toxicity of axitinib combined with 5-FU in nude mice bearing transplanted tumor of colon cancer LoVo cells.Methods Nude mouse models bearing LoVo colon cancer xenograft were randomized into vehicle control group,untreated control group,axitinib-treated group,5-FU-treated group and combined treatment group for corresponding treatments.The tumor dimensions,body weight and tumor weight were recorded,and the efficacy and toxicity were evaluated interms of complete remission(CR),partial remission(PR),tumor growth delay(TGD),mortality rate and net body weight loss.Results The combined treatment showed a significantly stronger efficacy than axitinib or 5-FU used alone.TGD of the combined treatment group was 16.73 days,longer than that of axitinib(8.53 days) and 5-FU(9.72 days) used alone.No mouse died during the treatments in the untreated control group,and 1 died in each of the other 4 groups.The mortality rate and weight loss were both less than 20%.One mouse had PR in axitinib-treated group and another in the combination treatment group.Axitinib,alone and in combination with 5-FU,reduced ABCG2 expression in the tumor tissue,and 5-FU has no such effect.Conclusion Combination of axitinib and 5-FU produces better antitumor effect than either drug used alone and is well tolerated in nude mice bearing colon cancer xenograft.

【关键词】 阿西替尼5-FU肠癌
【Key words】 axitinib5-FUcolon cancer
【基金】 广东省自然科学基金(S2011040003476);广东省卫生厅(A2011277)
  • 【文献出处】 南方医科大学学报 ,Journal of Southern Medical University , 编辑部邮箱 ,2012年06期
  • 【分类号】R735.3
  • 【被引频次】5
  • 【下载频次】231
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