乳腺癌细胞系采用维生素C和槲皮素序贯治疗可提高化疗药物的疗效。

Sequential Therapy of Breast Cancer Cell Lines with Vitamin C and Quercetin Improves the Efficacy of Chemotherapeutic Drugs.

作者信息

Ramezani Fatemeh, Samadi Nasser, Mostafavi-Pour Zohreh

机构信息

a Recombinant Protein Laboratory, Biochemistry Department , School of Medicine, Shiraz University of Medical Sciences , Shiraz , Iran.

b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.

出版信息

Nutr Cancer. 2017 Aug-Sep;69(6):881-891. doi: 10.1080/01635581.2017.1339813. Epub 2017 Jul 25.

DOI:10.1080/01635581.2017.1339813

PMID:28742385

Abstract

OBJECTIVE

Prevention by antioxidant agents including vitamin C (VC) and quercetin (QU), which are nontoxic, cost effective, and physiologically bioavailable, is a promising approach in breast cancer handling. The aim of this work is to investigate the influence of VC+QU on cytotoxicity profile of doxorubicin (DOX) plus paclitaxel (PAC) in breast cancer cells.

METHODS

The effect of each drug on its own or in combination was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Combination indexes were calculated using the Chou-Talalay method. Apoptosis and cell cycle analysis was investigated by flow cytometric assays.

RESULTS

Combination treatment with VC+QU plus drugs diminished IC value 2.28-7.7 and 10.5-66.6 fold in comparison with the drugs and PAC treatment alone, respectively, in all breast cancer cells and induced apoptosis at the early stages more than the treatment with the drugs alone (P<0.01). A marked reduction in Go/G1 and S phases was reported after combination therapy in MDA-MB 231 and MDA-MB 468 cells. MCF-7 cells demonstrated lower fractions of cells in S phase with no significant changes in G2/M phase (P < 0.01). The same treatment produced a significant increase in S and G2/M phases in A549 cells (P < 0.001).

CONCLUSION

Our results emphasized the importance of VC+QU in combination with the drugs to produce a synergistic antitumor effect in breast cancer cells.

摘要

目的

包括维生素C（VC）和槲皮素（QU）在内的抗氧化剂具有无毒、成本效益高和生理上可生物利用的特点，通过它们进行预防是乳腺癌治疗中一种很有前景的方法。这项工作的目的是研究VC+QU对乳腺癌细胞中阿霉素（DOX）加紫杉醇（PAC）细胞毒性谱的影响。

方法

通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）试验评估每种药物单独或联合使用的效果。使用Chou-Talalay方法计算联合指数。通过流式细胞术分析研究细胞凋亡和细胞周期。

结果

与单独使用药物和PAC治疗相比，在所有乳腺癌细胞中，VC+QU联合药物治疗分别使IC值降低了2.28 - 7.7倍和10.5 - 66.6倍，并且比单独使用药物治疗更早地诱导了细胞凋亡（P<0.01）。联合治疗后，MDA-MB 231和MDA-MB 468细胞的G0/G1期和S期明显减少。MCF-7细胞的S期细胞比例较低，G2/M期无显著变化（P < 0.01）。相同的治疗使A549细胞的S期和G2/M期显著增加（P < 0.001）。