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萎叶提取物增强5-氟尿嘧啶对结肠癌细胞HT29和HCT116的生长抑制作用
作者姓名:Pek Leng NG  ;Nor Fadilah RAJAB  ;Sue Mian THEN  ;Yasmin Anum MOHD YUSOF  ;Wan Zurinah WAN NGAH  ;Kar Yong PIN  ;Mee Lee LOOI
作者单位:[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
基金项目:Project supported by the Ministry of Higher Education, Malaysia (No. UKM-JJ-03-FRGS0044-2010) and Universiti Kebangsaan Ma- laysia (No. UKM -DPP-2014-131)
摘    要:研究目的:探讨萎叶(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,AnnexinV/PI染色法检测HT29和HCT116细胞的凋丁L=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:胡椒科  蒌叶  5-氟尿嘧啶  等效线图法  草药-药物相互作用

Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells
Pek Leng NG,;Nor Fadilah RAJAB,;Sue Mian THEN,;Yasmin Anum MOHD YUSOF,;Wan Zurinah WAN NGAH,;Kar Yong PIN,;Mee Lee LOOI.Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells[J].Journal of Zhejiang University Science,2014,15(8):692-700.
Authors:Pek Leng Ng  Nor Fadilah Rajab  Sue Mian Then  Yasmin Anum Mohd Yusof  Wan Zurinah Wan Ngah  Kar Yong Pin  Mee Lee Looi
Institution: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
Abstract:

Objective

The combination effect of Piper betle (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 (IC50 12.5 μmol/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.
Keywords:Piperaceae  Piper beUe L    5-Fiuorouracil  Isobologram analysis  Herb-drug interaction
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