乳腺癌耐药动物模型建立及咯萘啶(PND)逆转乳腺癌耐药的效果观察

Establishment of Breast Cancer Resistant Animal Model and Reversal of Drug Resistance of Breast Cancer by PND

目的探讨乳腺癌耐药动物模型建立及抗疟药咯萘啶(PND)逆转乳腺癌耐药效果。方法采用人耐药细胞MCF-7/ADM和乳腺细胞系MCF-7接种于裸鼠上,建立耐药单侧和肿瘤敏感模型。然后将裸鼠随机分为5组,各组为6只小鼠。对照组A组注射相应溶剂;对照组B组注射阿霉素;高剂量联合组腹腔注射咯萘啶(PND)4 mg/kg;中剂量联合组腹腔注射咯萘啶(PND)2 mg/kg:低剂量联合组腹腔注射咯萘啶(PND)1 mg/kg,耐药移植肿瘤接种后第9天开始给药,移植肿瘤接种后第6天开始给药,每隔3天给药1次,腹腔注射。观察接种后第6天的生长状况,对体积>100 mm3的成瘤进行收集。记录并对比各组裸鼠移植瘤生长的抑制以及裸鼠体重情况。结果与对照组B组对比,低剂量和中剂量联合组抑瘤率无明显差异(P>0.05);高剂量联合组抑瘤率明显更高,差异显著(P<0.05)。和对照组A组体重对比,中剂量(2 mg/kg)联合组、高剂量(4 mg/kg)联合组和对照组B组明显降低,差异显著(P<0.05);和对照组B组对比,高剂量(4 mg/kg)联合组治疗后小鼠体重明显降低,差异显著(P<0.05)。结论PND具有高效的逆转肿瘤MDR的作用,可作为一种新的肿瘤耐药逆转剂。

Objective To build breast cancer resistant animal model and study the effect of antimalarial drug PND reversing breast cancer drug resistance.Methods Human drug-resistant cell line MCF-7/ADM and breast cell line MCF-7 were inoculated into nude mice to establish drug-resistant unilateral and tumor sensitive models.Then the nude mice were randomly divided into 5 groups with 6 mice in each group.Control group A was injected with corresponding solvent;adriamycin was injected into control group B;In the high dose combined group,pyronaridine(PND)4 mg/kg was injected intraperitoneally;The medium dose combined group was intraperitoneally injected with pyronaridine(PND)2mg/kg;the low dose combined group was intraperitoneally injected with pyronaridine(PND)1mg/kg.The drug was administered on the 9th day after drug-resistant transplanted tumor inoculation,and on the 6th day after transplanted tumor inoculation.The drug was administered once every 3 days.The growth condition on the 6th day after inoculation was observed,and the tumorigenesis with volume>100 mm3 were collected.The growth inhibition of transplanted tumor and the body weight of nude mice in each group were recorded and compared.Results Compared with control group B,there was no significant difference in tumor inhibition rate between low dose and medium dose combined group(P>0.05);The tumor inhibitio0n rate of high-dose combined group was significantly higher,with significant difference(P<0.05).Compared with control group A,the middle dose(2 mg/kg)combined group,high dose(4mg/kg)combined group and control group B were significantly lower,with significant difference(P<0.05);Compared with the control group B,the weight of mice in the high dose(4mg/kg)combined group decreased significantly after treatment,and the difference was significant(P<0.05).Conclusion The PND unit have efficient reverse tumor MDR role,thus can be used as a new kind of tumor drug resistance reversal agents.