摘要
目的:探讨中药制剂穿琥宁对HCT-8/5-FU多药耐药细胞株的影响。方法:观察0.4,1.2和2.4mg·mL-1穿琥宁作用下的HCT-8/5-FU多药耐药细胞株生长曲线,MTT法检测上述浓度下的细胞抑制率。MTT法、流式细胞仪PI染色法检测穿琥宁与化疗药物5-氟尿嘧啶(5-FU)、顺铂(DDP)和阿霉素(ADM)联合作用下,对HCT-8-5-FU耐药细胞的毒性作用和凋亡率。流式细胞仪罗丹明染色法和PI染色法探讨穿琥宁的作用机制。结果:0.4mg·mL-1穿琥宁生长曲线与正常对照组无明显差别,1.2mg·mL-1穿琥宁对细胞生长有轻度抑制作用,2.4mg·mL-1浓度有一定抑制,但细胞仍可生长。MTT法检测0.4,1.2,2.4mg·mL-1穿琥宁作用下,HCT-8/5-FU耐药细胞株的抑制率分别为7.2%,13.2%,21%。1.2mg·mL-1穿琥宁与5-FU,DDP,AMD联合作用,与这3种化疗药物单独作用比较细胞凋亡率分别为54.2%/26.4%;42.6%/13.6%;30.8%/14.2%,差异显著(P<0.01)。罗丹明染色法提示穿琥宁的作用机制可能与影响P-170的活性有关。但穿琥宁本身并不诱导凋亡,对细胞周期也无影响。结论:低浓度穿琥宁对HCT-8/5-FU细胞无明显抑制作用;与5-FU,ADM,DDP联合作用,可增加上述化疗药物的毒性作用,使肿瘤细胞的凋亡率增高,其机制可能与抑制P-170功能有关。
Objective: To elucidate the effect of andrographolid (an extract essence from a medicinal herb:Andrographis paniculate ,AG) on HCT-8/5-FU multidrugs resistant colorectal cancer cell line. Methods:HCT-8/5-FU multidrugs resistant cell line was used and the resistant index of HCT-8/5-FU cells to 5-FU,ADM,DDP with or without the presence of 0.4,1. 2 and 2.4mg·mL-1 of AG, the growth curves and inhibition rate as well as apoptotic rate of HCT-8/5-FU at different concentra-tions of AG were evaluated by MTT and flow cy tometry. Rhodamine staining was used to investigate the possible mechanism involved by AG. Results: AG at low concentration showed weak inhibitory ef-fect on HCT-8/5-FU.However,a remarkable inhibitory and apoptotic rate was shown when co-admin-istered AG with 5-FU,ADM and DDP respectively. Interestingly,AG alone could not induce apoptosis and change the cell cycles. AG might affect the expression of P-170,which was indicated by rhodamine staining. Conclusion: AG may act as an chemosensitizer when co-administered with 5-FU,ADM and DDP,and the mechanism of reversal modulation of multidrug resistance by AG in HCT-8/5-FU resistant cell line may be related to its down- regulation of over-expression of P-170.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2004年第5期404-407,共4页
Chinese Journal of New Drugs
