体素内不相干运动成像在体检测人类结肠癌SW480裸鼠耐药性

In vivo intravoxel incoherent motion imaging in evaluation on drug resistance of human colon cancer SW480 in nude mice

目的探讨体素内不相干运动(IVIM)成像活体评价人类结肠癌SW480裸鼠耐药性及其可行性。方法对耐药组(n=5)和不耐药组(n=5)人类结肠癌SW480荷瘤裸鼠于肿瘤最长径大于1.50 cm后分别行IVIM DWI检查,测量肿瘤真扩散系数(D)、假扩散系数(D~*)及灌注分数(f)。处死荷瘤鼠,检测肿瘤坏死(HE染色)、凋亡(TUNEL法)及P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)、蛋白激酶C(PKC)蛋白表达(Western Blot),对IVIM参数和肿瘤蛋白表达情况进行相关分析。结果不耐药组D较耐药组增高(P<0.05),2组D~*和f差异无统计学意义(P均>0.05)。2组肿瘤组织坏死区域范围相似;耐药组细胞核较不耐药组增大,且细胞间排列更紧密,细胞密度较大。2组肿瘤细胞凋亡指数差异无统计学意义(P>0.05)。耐药组PKC、P-gp、MRP1蛋白表达均较不耐药组增加(P均<0.05)。肿瘤D值与P-gp、MRP1、PKC表达均呈负相关(P均<0.05)。结论 IVIM成像参数D值可能成为评估小鼠人类结肠癌SW480耐药性的指标。

Objective To explore drug resistance of human colon cancer SW480 tumor in nude mice with intravoxel incoherent motion (IVIM) imaging in vivo and its feasibility. Methods Nude mice with human colon cancer SW480 tumor in the resistant group ( n =5) and non-drug resistant group ( n =5) underwent IVIM imaging when the longest tumor diameter was greater than 1.50 cm, and true-diffusion coefficient (D), pseudo-diffusion coefficient (D *) and perfusion fraction (f) of the tumor were measured. Then the mice were sacrificed, and the protein expression (Western Blot) of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), protein kinase C (PKC), necrosis (HE stain), apoptosis (TUNEL) of tumors were detected. Correlation analysis on IVIM parameters and tumor protein expression was performed. Results The D value of non-resistance group was higher than that of drug-resistant group ( P <0.05). There was no statistical difference of D * nor f between the two groups (all P >0.05). Tumor necrosis areas of the two groups were similar, the nucleus of drug-resistant group was larger than that of non-resistant group, while cells were arranged more closely and cell density was larger. There was no statistical difference in the apoptotic index between the two groups ( P >0.05). Protein expression of PKC, P-gp and MRP1 in the drug-resistant group was higher than those in non-resistant group (all P <0.05). The D value was negatively correlated with the expression of P-gp, MRP1 and PKC (all P <0.05). Conclusion The D value of tumor in nude mice model may become a significant marker to in vivo evaluate drug resistance of nude mice with human colon cancer SW480 tumor.