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三苯氧胺逆转大肠癌多药耐药性的研究
探讨体内应用三苯氧胺(tamoxifen,TAM)对大肠癌多药耐药性(multidrug resistance, MDR)的影响及其与雌激素受体(ER)表达的关系。方法 制成3组人大肠癌裸鼠移植瘤模型：mdr1(+)ER(+)组、mdr1(+)ER(-)组及mdr1(-)组。各组再分成4个亚组：对照组、阿霉素(DOX)治疗组、TAM治疗组及TAM+DOX联合治疗组。结果 mdr(-)组中DOX组及TAM+DOX组于第2疗程末瘤体积及瘤重均小于对照组(P＜0.05)，TAM组与对照组差异无显著性(P＞0.05)；mdr1(+)/ER(+)组中TAM+DOX组的瘤体积及瘤重均显著小于对照组(P＜0.05)，DOX组、TAM组与对照组均无明显差异；mdr1(+)/ER(-)组结果与mdr1(+)/ER(+)组相似。结论 三苯氧胺在荷瘤裸鼠体内应用能逆转植入大肠癌MDR，与是否表达ER无明显相关。
The effects of tamoxifen on multidrug resistance of colon cancer in vivo SHEN Lizong, WU Wen xi.
（Department of General Surgery, The First Affiliated Hospital,
Nanjing Medical University, Nanjing 210029,China）
【Abstract】 Objective To evaluate the effects of tamoxifen (TAM) on multidrug resistance (MDR) of colon cancer in nude mice and the depends on expression of estrogen receptor (ER).Methods The human colon carcinomas tissues with mdr1(+)/ER(+), mdr1(+)/ER(-) or mdr1(-) expression respectively were planted subcutaneously in nude mice. All animal models were ided into 4 subgroups: doxorubicin (DOX), TAM, DOX plus TAM treated group and control group. The xenografts were measured after each course of treatment and removed at the end of the experiments for measurements of weight and mdr1 mRNA level.Results In the animals with mdr1(-) tumor the weight of tumor in DOX and TAM+DOX group were less than that of the control (P＜0.05) significantly. In the models with mdr1(+)/ER(+) tumor the weight of the tumor was not affected by DOX or TAM treatment. However, the tumor weight in TAM+DOX group was less than that of control(P＜0.01) significantly, similar to the result of models with mdr1 (+)/ER(-) tumor.Conclusion The expression of mdr1 corresponds to the sensitivity of colon cancer to antitumor drugs in vivo. TAM can reverse the MDR of colon cancer in nude mice, which is independent of the expression of ER.
【Key words】 Colon cancer; Multidrug resistance; Tamoxifen
多药耐药性(multidrug resistance，MDR)是影响肿瘤化疗效果的重要因素。现已证明MDR主要是由mdr1基因编码的P-糖蛋白(p-glycoprotein,Pgp)介导的。我们通过建立mdr1/Pgp表达阳性的人大肠癌裸鼠移植模型，对动物模型使用三苯氧胺(tamoxifen,TAM)，研究体内应用能否获得增强化疗敏感性的作用，以及其作用与雌激素受体(ER)表达的关系。
材料与方法
1.MDR及ER的检测：MDR的检测采用RT-PCR，以β2-MG为内参照进行半定量分析。ER的检测采用免疫组织化学法。
