恶性肿瘤化疗多药耐药动物模型的实验研究

Experimental research of the multidrug resistant animal model for malignant tumor chemotherapy

目的建立肿瘤多药耐药动物模型,为筛选有效逆转肿瘤多药耐药的药物及研究克服肿瘤耐药、提高化疗效果奠定基础。方法模拟恶性肿瘤细胞在人体内经化疗逐渐演化为多药耐药细胞的生理过程,利用BABL/c小鼠,腹腔接种S-180瘤细胞建成小鼠肿瘤动物模型,在低剂量阿霉素腹腔注射治疗下,经过15个周期的培育传代,获得了耐药的肿瘤细胞株S-180R。结果耐药细胞株对阿霉素的耐药性比亲本细胞株高66倍,对VP-16的耐药性高9倍;免疫细胞化学证实耐药细胞显示肿瘤多药耐药基因产物P-170糖蛋白过量表达;流式细胞仪荧光检测表明耐药细胞比亲本细胞排除药物的能力提高89倍。结论本研究成功地建立了S-180R耐药细胞株的肿瘤多药耐药动物模型,为进一步筛选有效逆转肿瘤多药耐药的药物及研究克服肿瘤耐药、提高化疗效果奠定了基础。

Objective：To develop the multidrug resistant animal model for malignant tumor chemotherapy and select drug or raise some other therapeutic strategies for reversing muhidrug resistance in vivo. Methods：The BABL/c mice inoculated by S-180 cells were injected with adriamycin in low dosage for 15 cycles. The muhidrug resistant animal model and resistant cells S-180R was achieved. Results：The Adriamycin of these cells was 66 times more than their parent cells. The resistance to a typical DNA topoisomerase Ⅱ inhibitor VP-16（Etoposide） was increased 9 times than their parent cells. Overexpression of muhidrug resistant gene （MDR gene） product P-glycoprotein was also demonstrated by immunohistochemical method. Furthermore, the ability of the resistant cells to reduce net cellular drug accumulation, which was measured with flow fluorescence cytometry, was 89 times higher than their parent cells. All of these confirmed that the resistance to adriamycin of S-180R cells were mainly due to the overexpression of p-glycoprotein. Conclusion：These new developed S-180 cells and mouse animal model would be useful to select drug or raise some other therapeutic strategies for reversing muhidrug resistance in vivo.