Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells  

蒌叶提取物增强5-氟尿嘧啶对结肠癌细胞HT29和HCT116的生长抑制作用(英文)

作　　者：Pek Leng NG Nor Fadilah RAJAB Sue Mian THEN Yasmin Anum MOHD YUSOF Wan Zurinah WAN NGAH Kar Yong PIN Mee Lee LOOI 

机构地区：[1]Department of Biomedical Sciences, Faculty of Allied Health, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz,50300 Kuala Lumpur, Malaysia [2]UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia (UKM), Jalan Yaacob Latiff, Bandar Tun Razak, Cheras,56000 Kuala Lumpur, Malaysia [3]School of Biomedical Science, University of Nottingham Malaysia Campus,43500 Semenyih, Selangor, Malaysia [4]Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz,50300 Kuala Lumpur, Malaysia [5]Forest Research Institute Malaysia (FRIM),52109 Kuala Lumpur, Kepong, Malaysia [6]School of Biosciences, Taylor’s University, Lakeside Campus,47500 Subang Jaya, Selangor, Malaysia

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2014年第8期692-700,共9页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the Ministry of Higher Education,Malaysia(No.UKM-JJ-03-FRGS0044-2010);Universiti Kebangsaan Malaysia(No.UKM-DPP-2014-131)

摘　　要：Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.研究目的:探讨蒌叶(PB)提取物对5-氟尿嘧啶(5-FU)抑制结肠癌细胞HT29和HCT116生长的影响。研究方法:HT29和HCT116细胞分别给予PB、5-FU以及两种药物联合治疗24小时,应用等效线图法分析PB和5-FU的药效学相互作用,Annexin V/PI染色法检测HT29和HCT116细胞的凋亡情况,高效液相色谱法排除PB和5-FU间任何可能的相互化学作用。重要结论:联合PB,低剂量5-FU可以在短时间内起到细胞毒作用,而单独应用PB或5-FU治疗较联合治疗可以诱导更多细胞发生凋亡。进一步采用等效线图法分析显示PB和5-FU的联合作用在抑制结肠癌细胞HT29和HCT116的生长中分别体现出协同和拮抗作用。因此可以认为在HT29细胞中,PB使得较低剂量5-FU发挥最大抑制结肠癌细胞生长效果,然而在HCT116细胞中,PB没有显著降低5-FU的药物浓度,说明PB和5-FU的相互作用不仅仅体现在诱导细胞凋亡方面。

关 键 词：PIPERACEAE Piper beUe L. 5-Fiuorouracil Isobologram analysis Herb-drug interaction 

分 类 号：R273[医药卫生—中西医结合] R285[医药卫生—中医肿瘤科]