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白藜芦醇和辣椒素联合用作食物补充剂可减少肿瘤生长,并挽救低剂量吉西他滨在胰腺癌模型中的全部疗效。

Resveratrol and capsaicin used together as food complements reduce tumor growth and rescue full efficiency of low dose gemcitabine in a pancreatic cancer model.

机构信息

INSERM U1035, Bordeaux, France; CHU de Bordeaux, Bordeaux, France.

Université de Bordeaux, Bordeaux, France; INSERM U1035, Bordeaux, France; CHU de Bordeaux, Bordeaux, France.

出版信息

Cancer Lett. 2017 Apr 1;390:91-102. doi: 10.1016/j.canlet.2017.01.002. Epub 2017 Jan 13.

DOI:10.1016/j.canlet.2017.01.002
PMID:28089829
Abstract

Pancreatic adenocarcinoma, highly resistant to all current anti-cancer treatments, necessitates new approaches promoting cell death. We hypothesized that combined actions of several Bioactive Food Components (BFCs) might provide specific lethal effect towards tumor cells, sparing healthy cells. Human tumor pancreatic cell lines were tested in vitro for sensitivity to resveratrol, capsaicin, piceatannol, and sulforaphane cytotoxic effects. Combination of two or three components showed striking synergetic effect with gemcitabine in vitro. Each BFC used alone did not affect pancreatic tumor growth in a preclinical in vivo model, whereas couples of BFCs had anti-tumor activity. In addition, tumor toxicity was similar using gemcitabine alone or a combination of BFCs and two thirds of gemcitabine dose. Moreover, BFCs enhanced fibrotic response as compared to gemcitabine treatment alone. Reactive oxygen species (ROS) and apoptosis increases were observed, while cell cycle was very mildly affected. This study raises the possibility to use BFCs as beneficial food complements in the therapy of pancreatic adenocarcinoma, especially for patients unable to receive full doses of chemotherapy.

摘要

胰腺腺癌对所有当前的抗癌治疗均具有高度抗性,因此需要采用新方法促进细胞死亡。我们假设,几种生物活性食品成分(BFC)的联合作用可能会对肿瘤细胞产生特异性的致死作用,而对健康细胞则没有影响。我们在体外测试了人类肿瘤胰腺细胞系对白藜芦醇、辣椒素、白皮杉醇和萝卜硫素细胞毒性作用的敏感性。两种或三种成分的联合使用在体外与吉西他滨具有显著的协同作用。单独使用每种 BFC 均不会影响临床前体内模型中的胰腺肿瘤生长,而 BFC 对则具有抗肿瘤活性。此外,与单独使用吉西他滨相比,BFC 联合使用可降低三分之二的吉西他滨剂量,同时也降低了肿瘤毒性。此外,与单独使用吉西他滨相比,BFC 还增强了纤维反应。观察到活性氧(ROS)和细胞凋亡增加,而细胞周期仅受到轻微影响。这项研究提出了将 BFC 用作胰腺腺癌治疗中有益的食物补充剂的可能性,特别是对于无法接受全剂量化疗的患者。

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