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小白菊内酯联合表阿霉素对 MDA-MB-468 乳腺癌细胞的抗癌和促凋亡作用。

Anticancer and apoptotic activities of parthenolide in combination with epirubicin in mda-mb-468 breast cancer cells.

机构信息

Department of Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran.

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Mol Biol Rep. 2020 Aug;47(8):5807-5815. doi: 10.1007/s11033-020-05649-3. Epub 2020 Jul 20.

Abstract

Breast cancer is the most common malignancy in women worldwide. Unfortunately, current therapeutic methods are not completely efficient. Hence, combination therapy with medicinal plants has attracted several kinds of research. In the current study, we aimed to investigate the apoptotic and anti-cancer effect of Parthenolide in combination with Epirubicin in the MDA-MB-468 breast cancer cell line. In this study,  the anti-proliferative and pro-apoptotic effect of Parthenolide in combination with Epirubicin and without it, in the MDA-MB-468 cell line have been assessed by MTT test, Hoescht staining and flow cytometry methods. Our outcomes showed that Parthenolide treatment in the present of Epirubicin led to a decrease in the minimum toxic concentration of Parthenolide and Epirubicin in comparison with individual treatments. Then, to achieve a likely molecular mechanism of mentioned drugs Bax and Bcl2 expression level evaluated by Real-time PCR and subsequently, Western blotting has been estimated the protein level of Caspase 3. Our data indicated that the treatment of cells with Parthenolide led to up-regulation of Bax and downregulation of Bcl2 at mRNA level. Moreover, Parthenolide treatment led to the obvious alternation of Caspase3 protein level. These results indicated that Parthenolide in combination with Epirubicin have significant cytotoxicity due to targeting the main regulators of apoptosis. Hence, according to lack of cytotoxicity of Parthenolide on normal cells that lead to reduction of drug side effects, it could be suggested as an adjuvant therapy with Epirubicin after complementary research on animal model and clinical trial.

摘要

乳腺癌是全球女性最常见的恶性肿瘤。不幸的是,目前的治疗方法并不完全有效。因此,药用植物的联合治疗吸引了多种研究。在本研究中,我们旨在研究小白菊内酯与表柔比星联合应用对 MDA-MB-468 乳腺癌细胞系的凋亡和抗癌作用。在这项研究中,通过 MTT 试验、Hoescht 染色和流式细胞术评估了小白菊内酯与表柔比星联合应用和不联合应用对 MDA-MB-468 细胞系的抗增殖和促凋亡作用。我们的结果表明,与单独治疗相比,小白菊内酯与表柔比星联合应用可降低小白菊内酯和表柔比星的最小毒性浓度。然后,为了确定上述药物 Bax 和 Bcl2 表达水平的可能分子机制,通过 Real-time PCR 评估,随后通过 Western blotting 评估 Caspase 3 的蛋白水平。我们的数据表明,小白菊内酯处理可导致 Bax 的上调和 Bcl2 的下调。此外,小白菊内酯处理导致 Caspase3 蛋白水平的明显改变。这些结果表明,小白菊内酯与表柔比星联合应用具有显著的细胞毒性,因为它针对凋亡的主要调节剂。因此,根据小白菊内酯对正常细胞无细胞毒性,可降低药物的副作用,建议在动物模型和临床试验中补充研究后,将其作为表柔比星的辅助治疗方法。

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