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单独使用二甲双胍以及二甲双胍与依托泊苷和表柔比星联合使用对作为甲状腺癌细胞系的B-CPAP和SW细胞的增殖、凋亡、坏死及迁移的影响。

Effect of metformin alone and in combination with etoposide and epirubicin on proliferation, apoptosis, necrosis, and migration of B-CPAP and SW cells as thyroid cancer cell lines.

作者信息

Ghavami Ghazaleh, Kiasari Ramin Ebrahimi, Pakzad Faezeh, Sardari Soroush

机构信息

Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, I.R. Iran.

出版信息

Res Pharm Sci. 2023 Jan 19;18(2):185-201. doi: 10.4103/1735-5362.367797. eCollection 2023 Apr.

Abstract

BACKGROUND AND PURPOSE

There has not been a comprehensive study on the simultaneous effects of metformin, etoposide, and epirubicin on thyroid cancer cells. Hence, the current research proposed the study on the effect of metformin alone and in combination with etoposide and epirubicin on the rate of proliferation, apoptosis, necrosis, and migration against B-CPAP and SW-1736 cells as thyroid cancer cell lines.

EXPERIMENTAL APPROACH

MTT-based proliferation assay, combination index method, flow cytometry, and scratch wound healing assays were used to evaluate the simultaneous effects of the three approved drugs against thyroid cancer cells.

FINDINGS/RESULTS: This study showed that the toxic concentration of metformin on normal Hu02 cells was more than 10 folds higher than B-CPAP and SW cancerous cells. Metformin in combination with epirubicin and etoposide could increase percentages of B-CPAP and SW cells in early and late apoptosis and necrosis phases in comparison with their single concentrations, significantly. Metformin in combination with epirubicin and etoposide could arrest the S phase in B-CPAP and SW cells, significantly. Metformin in combination with epirubicin and etoposide could reduce ~100% migration rate, whereas single concentrations of epirubicin and etoposide could reduce ~50% migration rate.

CONCLUSION AND IMPLICATION

Combined treatment of metformin with anticancer drugs epirubicin and etoposide can increase the mortality in thyroid cancer cell lines and reduce the toxicity of these drugs on the normal cell line, which could be the starting point for proposing a new combination strategy in the therapy of thyroid cancer to induce more potency and reduce acute toxicity.

摘要

背景与目的

目前尚未有关于二甲双胍、依托泊苷和表柔比星对甲状腺癌细胞同时作用的全面研究。因此,本研究旨在探讨二甲双胍单独使用以及与依托泊苷和表柔比星联合使用对甲状腺癌细胞系B-CPAP和SW-1736细胞增殖、凋亡、坏死及迁移率的影响。

实验方法

采用基于MTT的增殖试验、联合指数法、流式细胞术和划痕伤口愈合试验来评估这三种获批药物对甲状腺癌细胞的联合作用。

研究结果

本研究表明,二甲双胍对正常Hu02细胞的毒性浓度比对B-CPAP和SW癌细胞高10倍以上。与单一药物浓度相比,二甲双胍联合表柔比星和依托泊苷可显著增加B-CPAP和SW细胞在早期和晚期凋亡及坏死阶段的比例。二甲双胍联合表柔比星和依托泊苷可显著使B-CPAP和SW细胞停滞于S期。二甲双胍联合表柔比星和依托泊苷可使迁移率降低约100%,而单一浓度的表柔比星和依托泊苷可使迁移率降低约50%。

结论与意义

二甲双胍与抗癌药物表柔比星和依托泊苷联合治疗可提高甲状腺癌细胞系的死亡率,并降低这些药物对正常细胞系的毒性,这可能是提出一种新的联合治疗策略以增强疗效并降低急性毒性的甲状腺癌治疗方案的起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f750/9976061/f4ff2ee3c949/RPS-18-185-g003.jpg

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