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桦木酸与两种紫杉烷类化合物在体外对四种人恶性黑素瘤细胞系的协同作用。

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines.

机构信息

Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.

Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-090 Lublin, Poland.

出版信息

Int J Mol Sci. 2022 Aug 25;23(17):9641. doi: 10.3390/ijms23179641.

DOI:10.3390/ijms23179641
PMID:36077036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456196/
Abstract

The incidence of melanoma is steadily increasing worldwide. Melanoma is the most lethal skin cancer, and new therapeutic methods are being sought. Our research aimed to investigate the cytotoxic and antiproliferative effects of betulinic acid in vitro, used alone and in combination with taxanes (paclitaxel, docetaxel) in four melanoma cell lines. Isobolographic analysis allowed us to assess the interactions between these compounds. Betulinic acid had no cytotoxic effect on normal human keratinocyte HaCaT cells; the amount of LDH released by them was significantly lower compared to melanoma cell lines. The present study shows that betulinic acid significantly inhibits the growth of melanoma cell lines in vitro. The IC50 values of betulinic acid ranged from 2.21 µM to 15.94 µM against the four melanoma lines. Co-treatment of betulinic acid with paclitaxel or docetaxel generated desirable drug-drug interactions, such as an additive and additive with a tendency to synergy interactions.

摘要

黑色素瘤的发病率在全球范围内呈稳步上升趋势。黑色素瘤是最致命的皮肤癌,因此正在寻求新的治疗方法。我们的研究旨在研究桦木酸在体外的细胞毒性和抗增殖作用,单独使用以及与紫杉醇(紫杉醇、多西紫杉醇)联合使用对四种黑色素瘤细胞系的影响。等辐射分析允许我们评估这些化合物之间的相互作用。桦木酸对正常人角质形成细胞 HaCaT 细胞没有细胞毒性作用;与黑色素瘤细胞系相比,它们释放的 LDH 量明显更低。本研究表明桦木酸可显著抑制体外黑色素瘤细胞系的生长。桦木酸对四种黑色素瘤细胞系的 IC50 值范围为 2.21µM 至 15.94µM。桦木酸与紫杉醇或多西紫杉醇联合治疗产生了理想的药物相互作用,如相加和相加有协同作用的趋势。

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