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韦地酮与顺铂联用对 HeLa 细胞系的协同细胞毒性作用：一项新发现。

Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding.

机构信息

Discipline of Biomedical Sciences, Sydney Medical School, The University of Sydney, Cumberland Campus, Sydney, NSW, Australia.

Department of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.

出版信息

Drug Des Devel Ther. 2020 Sep 22;14:3841-3852. doi: 10.2147/DDDT.S261321. eCollection 2020.

DOI:10.2147/DDDT.S261321
PMID:33061291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7519871/
Abstract

CONTEXT AND OBJECTIVE

Cisplatin is a platinum drug in current clinical use for the treatment of cervical cancer. However, drug toxicity and resistance are its two major limitations. The aim of this investigation was to test the cytotoxic activity of potential phytochemicals alone and in combination with cisplatin in cervical cancer cells.

METHODS

In this study, cytotoxicity of phytochemicals including wedelolactone (WDL), betulinic acid (BA) and epigallocatechin gallate (EGCG) was investigated in human cervical cancer cell line HeLa through 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combined drug action resulting from the combination of cisplatin with WDL and BA was investigated in the same cell line through median effect principle. The combination index (CI) was taken as a measure of combined drug action.

RESULTS

BA resulted in synergistic outcome when co-administered with cisplatin at 0/0 time; (bolus administration) while administration of either drug (cisplatin or BA) four hours before the other (0/4 or 4/0) resulted in antagonistic action. WDL, on the other hand, was found out to be synergistic at any of the applied sequence of drug administration (0/0, 0/4 or 4/0).

DISCUSSION AND CONCLUSION

This is the first study reporting cytotoxic activity of WDL in HeLa cells either as single agent or in combination with cisplatin. These results support the idea that sequential combination of cisplatin with WDL and BA may work effectively in cervical cancer cells.

摘要

背景和目的

顺铂是目前临床上用于治疗宫颈癌的铂类药物。然而，其毒性和耐药性是其两大主要限制。本研究旨在测试潜在植物化学物质单独及与顺铂联合对宫颈癌细胞的细胞毒性作用。

方法

在这项研究中，通过 3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-四唑溴盐（MTT）还原试验，研究了植物化学物质包括芫花内酯（WDL）、桦木酸（BA）和表没食子儿茶素没食子酸酯（EGCG）对人宫颈癌 HeLa 细胞系的细胞毒性作用。通过中值效应原理，在同一细胞系中研究了顺铂与 WDL 和 BA 联合用药的联合药物作用。采用合并指数（CI）作为联合药物作用的衡量标准。

结果

BA 与顺铂联合应用时，在 0/0 时间点（冲击给药）时产生协同作用；而在其他两种药物（顺铂或 BA）给药 4 小时之前（0/4 或 4/0）给药时产生拮抗作用。另一方面，WDL 无论在何种给药顺序（0/0、0/4 或 4/0）下，均显示出协同作用。

讨论和结论

这是首次报道 WDL 对 HeLa 细胞具有细胞毒性作用的研究，无论是单独应用还是与顺铂联合应用。这些结果支持这样一种观点，即顺铂与 WDL 和 BA 的序贯联合可能在宫颈癌细胞中有效发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/76a3f64ea069/DDDT-14-3841-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/62f3642dee32/DDDT-14-3841-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/209772b08270/DDDT-14-3841-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/fcbbfb54e149/DDDT-14-3841-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/7edb1bda2218/DDDT-14-3841-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/b2d7a293d284/DDDT-14-3841-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/0b4520fd1cab/DDDT-14-3841-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/67e1cd8af5f3/DDDT-14-3841-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/24e6fb6a6d14/DDDT-14-3841-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/cb958ccafb51/DDDT-14-3841-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/432dcf27a7bb/DDDT-14-3841-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/9314eb054a8a/DDDT-14-3841-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/76a3f64ea069/DDDT-14-3841-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/62f3642dee32/DDDT-14-3841-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/209772b08270/DDDT-14-3841-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/fcbbfb54e149/DDDT-14-3841-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/7edb1bda2218/DDDT-14-3841-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/b2d7a293d284/DDDT-14-3841-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/0b4520fd1cab/DDDT-14-3841-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/67e1cd8af5f3/DDDT-14-3841-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/24e6fb6a6d14/DDDT-14-3841-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/cb958ccafb51/DDDT-14-3841-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/432dcf27a7bb/DDDT-14-3841-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/9314eb054a8a/DDDT-14-3841-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/7519871/76a3f64ea069/DDDT-14-3841-g0012.jpg

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Betulinic acid and the pharmacological effects of tumor suppression (Review).桦木酸及其肿瘤抑制药理作用（综述）
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Molecular mechanisms of cisplatin resistance in cervical cancer.宫颈癌顺铂耐药的分子机制
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Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling.水飞蓟宾葡甲胺通过降低Akt/mTOR信号传导来抑制乳腺癌诱导的破骨细胞生成。
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