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白藜芦醇通过调节内源性凋亡增加乳腺癌MDA-MB-231细胞系对顺铂的敏感性。

Resveratrol increases the sensitivity of breast cancer MDA-MB-231 cell line to cisplatin by regulating intrinsic apoptosis.

作者信息

Özdemi R Filiz, Sever Arda, Keçeci Yüksel Öğünç, Incesu Zerrin

机构信息

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

出版信息

Iran J Basic Med Sci. 2021 Jan;24(1):66-72. doi: 10.22038/ijbms.2020.50485.11501.

Abstract

OBJECTIVES

Breast cancer is one of the most common types of cancer. Chemotherapeutic agents used during treatment induce cytotoxic effects also on normal cells in the tissues. Anti-oxidants used in combination with chemotherapeutic agents have been shown to reduce toxicity on normal cells to a minimum, and some anti-oxidant substances have chemotherapeutic effects. Cisplatin (CDDP) is a platinum class drug that is used clinically in the treatment of many cancers. Resveratrol (RSV) is a natural polyphenol with potent anti-oxidant and anticancer properties. In this study, we aimed to investigate apoptotic effects of using cisplatin and RSV alone or in combined treatment of MDA-MB-231 cells.

MATERIALS AND METHODS

The cytotoxic effects of the drugs on MDA-MB-231 cells were determined by MTT method. Subsequently, the change in CDDP-induced apoptotic effect after RSV addition was examined using the AnnexinV FITC labeling, and TUNEL staining method. Activation of caspase-9, -3 in MDA-MB-231 cells was measured by flow cytometer. The mitochondrial membrane potential (MMP), the major factor on the intrinsic pathway, was measured using flowcytometry.

RESULTS

The combined dose (23 μM CDDP + 72 μM RSV) produced more cytotoxicity than the agents used alone, leading to early apoptosis (8.2%), 31% depolarization, and 23% DNA fragmentation. Caspase-9 was found to be 30.5% in this combined group and caspase-3 was 26.3%.

CONCLUSION

RSV, an effective anti-oxidant, and CDDP as an effective drug in cancer treatment, were found to increase apoptosis when given in the MDA-MB-231 cell.

摘要

目的

乳腺癌是最常见的癌症类型之一。治疗期间使用的化疗药物对组织中的正常细胞也会产生细胞毒性作用。已证明与化疗药物联合使用的抗氧化剂可将对正常细胞的毒性降至最低,并且一些抗氧化物质具有化疗作用。顺铂(CDDP)是一种铂类药物,临床上用于治疗多种癌症。白藜芦醇(RSV)是一种具有强大抗氧化和抗癌特性的天然多酚。在本研究中,我们旨在研究单独使用顺铂和RSV或联合治疗MDA-MB-231细胞的凋亡作用。

材料与方法

采用MTT法测定药物对MDA-MB-231细胞的细胞毒性作用。随后,使用膜联蛋白V FITC标记和TUNEL染色法检测添加RSV后CDDP诱导的凋亡作用的变化。通过流式细胞仪测量MDA-MB-231细胞中caspase-9、-3的激活情况。使用流式细胞术测量内在途径的主要因素线粒体膜电位(MMP)。

结果

联合剂量(23μM CDDP + 72μM RSV)比单独使用的药物产生更强的细胞毒性,导致早期凋亡(8.2%)、31%的去极化和23%的DNA片段化。在该联合组中发现caspase-9为30.5%,caspase-3为26.3%。

结论

发现有效的抗氧化剂RSV和作为癌症治疗有效药物的CDDP在给予MDA-MB-231细胞时可增加细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46c/7894626/590d99a16db7/IJBMS-24-066-g001.jpg

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