磁共振弥散成像活体检测rAd/p53治疗人类结肠癌荷瘤裸鼠早期疗效

Early therapeutic response of rAd/p53 in human colon cancer model using MR-DWI

目的:运用磁共振弥散成像(DWI)研究rAd/p53治疗人类结肠癌荷瘤裸鼠的早期改变,探索MR-DWI活体无创评价rAd/p53早期抗癌疗效的标记物。方法:52只人类结肠癌SW480荷瘤BALB/c裸小鼠随机分成2组:对照组,rAd/p53治疗组。于假治疗或治疗后24 h、48 h、72 h、120 h、168 h各组分别随机取5只荷瘤鼠行MR-DWI。随后处死荷瘤鼠,即切下肿瘤,检测肿瘤的p53蛋白表达(western blot)、凋亡(TUNNEL)。结果:rAd/p53治疗组在观察时间点肿瘤ADC值较对照组增加、EADC值较对照组降低。治疗组在观察时间点肿瘤凋亡较对照组增加,p53蛋白表达均较对照组增高。ADC值与肿瘤细胞凋亡范围呈正相关(0.205 3,0.000 0)、与肿瘤p53表达呈正相关(0.203 8,0.000 0);EADC值与肿瘤细胞凋亡范围呈负相关(-0.318 4,0.000 0)、与肿瘤p53表达呈负相关(-0.328 0,0.000 0)。结论:ADC值和EADC值在治疗后24 h即可出现有统计意义的改变,可作为rAd/p53治疗肿瘤早期疗效评价的生物标记物。

Objective： To study the early response of rAd/p53 in nude mice bearing human colon cancer model of SW480 using MR-DWI.Methods： The tumor pieces of human colon cancer SW480 were injected subcutaneously into 52 nude mice.These mice were divided randomly into two groups that is the control group and the therapeutic group.rAd/p53 was injected into the tumor of the mice in the therapeutic group,while saline was injected into the tumor of the mice in the control group.At 24 h,48 h,72 h,120 h and 168 h after treatment,MR-DWI was performed with 1.5T MR system for five mice at each time point of each group.Then the mice were sacrificed and the tumor in which were removed.P53 expression（western blot） and apoptosis of tumor（TUNNEL） were assessed.Results： ADC values of tumors in each time point after rAd/p53 injection were higher than those of the control groups.EADC values after rAd/p53 injection were lower than those of the control groups.p53 expression and apoptosis of the tumor in the therapeutic group were higher than that of the control groups.ADC value showed positive correlations with the extent of apoptosis of tumor cells and showed positive correlation with p53 expression.EADC value showed negative correlations with the apoptotic extent of tumor cells and negative correlation with p53 expression.Conclusions： ADC value and EADC value change significantly at 24 h after treatment.They can be used as biomarker in evaluation of early response of rAd/p53 in the treatment of tumor.