谢琦，吴敏仪，杨逸铭，张鼎旋，雷正贤，张静，许进，钟维德



扩散加权MRI活体评价外源野生型P53逆转SW480/5-FU人类结肠癌效果

谢琦1*，吴敏仪1，杨逸铭1，张鼎旋1，雷正贤1，张静4，许进2，钟维德3

[摘要]目的 探索扩散加权MRI (DWI)活体评价rAd/p53逆转耐5-FU结肠癌SW480/5-FU对5-FU耐药性效果的可能性。材料与方法 100只结肠癌SW480/5-FU荷瘤裸鼠随机分成4组，对照组、5-FU组、rAd/p53组、rAd/p53+5-FU组。各组在治疗后24 h、48 h、72 h、120 h、168 h分别随机取5只荷瘤鼠行DWI检查，随后处死荷瘤鼠，切下肿瘤检测肿瘤细胞凋亡(TUNNEL法)。结果 rAd/p53组与rAd/p53+5-FU组在观察时间点肿瘤ADC值均较对照组增加，与对照组比较差别有统计学意义(P＜0.05)；rAd/p53组与rAd/p53+5-FU组在观察时间点肿瘤凋亡较对照组增加；rAd/p53+5-FU组在观察时间点肿瘤肿瘤凋亡和ADC值较rAd/p53组高。ADC值与肿瘤凋亡呈正相关。结论 ADC值能活体评价外源野生型p53逆转SW480/5-FU耐药性早期疗效。

[关键词]基因，p53；结肠肿瘤；氟尿嘧啶；弥散磁共振成像；动物实验

广东省自然科学基金(编号：2015A03 0313732)

作者单位：

1.广州医科大学附属广州市第一人民医院南沙医院 广州市南沙中心医院医学影像科，广州 511457

2.广州医科大学附属广州市第一人民医院病理科，广州 510180

3.广州医科大学附属广州市第一人民医院临床分子医学及分子诊断实验室，广州 510180

4.中山大学肿瘤防治中心病理科，广州 510180

谢琦，E-mail：xieqi8@yeah.net

接受日期：2015-11-07

谢琦, 吴敏仪, 杨逸铭, 等.扩散加权MRI活体评价外源野生型P53逆转SW480/5-FU人类结肠癌效果.磁共振成像, 2016, 7(1): 56–61.

In vivo detection of the reversal effects using rAd/p53 to human colon cancer in mice with diffusion-weighted magnetic resonance imaging

XIE Qi1*, WU Min-yi1, YANG Yi-ming1, ZHANG Ding-xuan1, LEI Zheng-xian1, ZHANG Jing4, XU Jin2, ZHONG Wei-de3

1Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People’s Hospital, Guangzhou Medical University, Guangzhou 511457, China.

2Department of Pathology, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China

3Clinical molecular medicine and molecular diagnostics laboratories, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China

4Department of Pathology, Sun yat-Sen University Cancer center, Guangzhou 510080, China

*Correspondence to: Xie Q, E-mail: xieqi8@yeah.net

Received 1 Oct 2015, Accepted 7 Nov 2015

ACKNOWLEDGMENTS Natural Science Foundation of Guangdong Province (No.2015A030313732).

Abstract Objective: To investigate the potential of diffusion-weighted magnetic resonance imaging (DWI) to detect the reversal effects of rAd/p53 for 5-FU resistance of human colon cancer in vivo.Materials and Methods: One hundred nude mice with human colon cancer SW480/5-Fu (5-Fu resistance) were randomly assigned into four groups: control group, 5-FU group, rAd/p53 group, rAd/p53+5-FU.At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were selected randomly from each group and given DWI examinations.Then these mouse models were sacrificed with an overdose of anesthetic.Their tumors were removed and detected apoptosis (TUNNEL).Results: The ADC values at the edge area of the tumor in rAd/p53 and rAd/p53+5-FU groups were significantly higher than that of the control groups at the observed time points (P＜0.05).The area ratios of tumor cell apoptosis in the rAd/p53+5-FU and rAd/p53 group were larger than that of control groups at the observed time point.The area ratios of tumor cell apoptosis and the ADC values in the rAd/p53+5-FU group were larger than that of rAd/p53 group at the observed time point.The ADC values of tumors were positively correlated with the area ratios of tumor cell apoptosis.Conclusions: The ADC value can evaluate the reversal effects of drug resistance with rAd/p53 in early stage of therapy in vivo.

Key words Genes, p53; Colonic neoplasms; Fluorouracil; Diffusion magnetic resonance imaging; Animal experimentation

本课题组在前期研究的结果中证实，扩散加权MRI (diffusion-weighted MRI，DWI)活体检测rAd/p53治疗人类结肠癌荷瘤裸鼠24 h即可以出现具有统计学意义的改变[1]。同时也发现，rAd/p53+5-FU治疗非耐药SW480结肠癌荷瘤裸鼠，可以加速肿瘤细胞的凋亡及提高p53蛋白的表达[2-3]。……