氯化两面针碱体外逆转KB/ADM细胞多药耐药性的研究  

Reversion of Multi Drug Resistance by Nitidine Chloride on KB/ADM Cell

作　　者：张华君[1] 刘华钢[1] 梁燕[1] 冯燕英[1] 李俊威[1] 

机构地区：[1]广西医科大学药学院,南宁530021

出　　处：《中国实验方剂学杂志》2015年第7期87-90,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81260657)

摘　　要：目的:探讨氯化两面针碱(nitidine chloride,NC)对人口腔鳞癌耐阿霉素(ADM)细胞株KB/ADM多药耐药性(MDR)的逆转作用,开发低毒高效的抗肿瘤药物多药耐药逆转剂。方法:人口腔鳞癌多药耐药细胞KB/ADM常规培养至细胞数为1×106,随机分为多药耐药细胞组(KB/ADM细胞组),阳性药物维拉帕米组(VRP,5μmol·L-1),NC低剂量组(0.375mg·L-1),NC中剂量组(0.75 mg·L-1),NC高剂量组(1.5 mg·L-1)5组,每组3个平行样本。分别加入同体积的培养基,5μmol·L-1VRP,0.375,0.75,1.5 mg·L-1NC处理48 h,MTT法分别检测各组细胞对化疗药物ADM,长春新碱(VCR),依托泊苷(VP-16),羟基喜树碱(HCPT)敏感性;流式细胞仪检测P糖蛋白的表达;RT-PCR法检测多药耐药基因-1(MDR1)的表达。结果:与多药耐药细胞组比较,阳性药物VRP组,NC低、中、高剂量组KB/ADM细胞对ADM,VCR,VP-16,HCPT的IC50值明显下降(P<0.01,P<0.05);阳性药物VRP组,NC低、中、高剂量组KB/ADM细胞P糖蛋白的表达分别为(10.60±1.11)%,(68.57±2.56)%,(28.29±1.98)%,(8.03±1.46)%,与多药耐药细胞组(97.33±1.61)%比较明显下降(P<0.01);阳性药物VRP组、NC低、中、高剂量组分别使KB/ADM的多药耐药性基因(MDR1)相对表达下降39%,22%,46%,69%(P<0.01)。结论:氯化两面针碱能有效逆转KB/ADM多药耐药性,具有良好的抗肿瘤药物多药耐药逆转作用。Objective： To investigate the reversal effect of nitidine chloride （NC） on human oral squamous cell carcinoma KB/adriamycin （ADM）. Method： The KB/ADM cells were cultured conventionally to 1 ×10^6, randomly divided into five groups： KB/ADM cells group, positive control verapamil group （VRP, 5μmol·L^-1）, low dose group of NC （0.375 mg·L^-1）, middle dose group of NC （0.75 mg·L^-1）, high dose group of NC （ 1.5 mg ·L^-1） , 3 parallel samples each. These groups were respectively added to the same volume of culture medium, 5μmol·L^-1 VRP, 0.375, 0.75, 1.5 mg ·L^-1 NC for 48 h. The cell sensitivity to chemotherapeutic drugs was demonstrated by MTT. The effect of NC on p-glyco protein （P-gp） expression was analyzed by flow cytometry. Muhidrug resistance gene-1 （MDR-1） expression was detected by RT-PCR. Result： Compared with KB/ADM ceils group, the IC50 value of positive control VRP group, low dose, middle dose and high dose group of NC to ADM, vincristine （VCR）, estoposide （VP-16）, hydroxycamptothecin （HCPT） were decreased significantly （P 〈 0. 01, P 〈 0. 05）. The P-gp expressions in VRP group, low, middle and high dose group with NC were respectively （10.60±1.11）%, （68.57±2.56）%, （28.29±1.98）%, （8.03±1.46）%, compared with KB/ADM cells group （97.33 ± 1.61）%, all of them were decreased significantly （P 〈0. 01）. The MDRI-mRNA expressions of positive VRP group, low dose, middle dose and high dose group with NC decreased by 39%, 22%, 46%, 69% （P 〈 0. 01） compared with KB/ADM cells group. Conclusion： NC can reverse the multidrug resistance of KB/ADM.

关 键 词：氯化两面针碱 KB/ADM细胞 多药耐药性 

分 类 号：R285.5[医药卫生—中药学]