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5-氟尿嘧啶通过 DNA 损伤和 MAPK 信号通路增加白藜芦醇在人结直肠癌细胞中的化学预防潜力。

5-fluorouracil increases the chemopreventive potentials of resveratrol through DNA damage and MAPK signaling pathway in human colorectal cancer cells.

机构信息

KIIT School of Biotechnology, KIIT University, Orissa, India.

出版信息

Oncol Res. 2011;19(7):311-21. doi: 10.3727/096504011x13079697132844.

DOI:10.3727/096504011x13079697132844
PMID:21936401
Abstract

Resveratrol (Res) can modulate multiple cellular pathways relevant for tumorigenesis but is less effective in colon cancer compared to breast cancer. To increase the chemopreventive potential of Res in combination with 5-fluorouracil (5-FU), a systematic study was carried out in colon cancer cells. HCT-116 cells were treated with Res and 5-FU and several cell-based assays, such as MTT, clonogenic, wound healing, DAPI, comet assay, and Western blot, were performed. A significant inhibition of cell proliferation, migration, and increased apoptosis were observed when moderate concentration of Res (15 microM) was associated with very low concentration of 5-FU (0.5 microM). This combination caused apoptosis by blocking the cells at S phase and enhanced the DNA damage. Expression levels of p-JNK and p-p38 were increased without affecting pERK. 5-FU could be used as a therapeutic modality to improve efficacy of Res-based chemotherapy against colon cancer.

摘要

白藜芦醇(Res)可以调节与肿瘤发生相关的多种细胞途径,但在结肠癌中的效果不如乳腺癌。为了提高白藜芦醇与 5-氟尿嘧啶(5-FU)联合的化学预防潜力,在结肠癌细胞中进行了系统研究。用白藜芦醇和 5-FU 处理 HCT-116 细胞,并进行了几种基于细胞的测定,如 MTT、集落形成、划痕愈合、DAPI、彗星试验和 Western blot。当中等浓度的白藜芦醇(15 μM)与非常低浓度的 5-FU(0.5 μM)联合使用时,观察到细胞增殖、迁移的显著抑制和凋亡的增加。这种组合通过阻断细胞在 S 期来诱导细胞凋亡,并增强 DNA 损伤。增加了 p-JNK 和 p-p38 的表达水平,而不影响 pERK。5-FU 可作为一种治疗方式,以提高基于白藜芦醇的化疗对结肠癌的疗效。

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