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顺铂在癌症治疗中的作用:分子作用机制

Cisplatin in cancer therapy: molecular mechanisms of action.

作者信息

Dasari Shaloam, Tchounwou Paul Bernard

机构信息

Cellomics and Toxicogenomics Research Laboratory, NIH/NIMHD RCMI-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18750, Jackson, MS 39217, USA.

Cellomics and Toxicogenomics Research Laboratory, NIH/NIMHD RCMI-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18750, Jackson, MS 39217, USA.

出版信息

Eur J Pharmacol. 2014 Oct 5;740:364-78. doi: 10.1016/j.ejphar.2014.07.025. Epub 2014 Jul 21.


DOI:10.1016/j.ejphar.2014.07.025
PMID:25058905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4146684/
Abstract

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects.

摘要

顺铂,又称顺式铂或顺二氯二氨铂(II),是一种著名的化疗药物。它已被用于治疗多种人类癌症,包括膀胱癌、头颈癌、肺癌、卵巢癌和睾丸癌。它对各种类型的癌症都有效,包括 carcinomas、生殖细胞肿瘤、淋巴瘤和肉瘤。其作用方式与其与DNA上嘌呤碱基交联的能力有关;干扰DNA修复机制,导致DNA损伤,随后诱导癌细胞凋亡。然而,由于耐药性以及许多不良副作用,如严重的肾脏问题、过敏反应、对感染的免疫力下降、胃肠道疾病、出血和听力损失(尤其是在年轻患者中),其他含铂抗癌药物,如卡铂、奥沙利铂等,也已被使用。此外,顺铂与其他药物的联合疗法已被高度重视,以克服耐药性并降低毒性。这篇综述重点介绍了顺铂及相关铂类药物的物理化学性质,并讨论了其(单独或与其他药物联合)用于治疗各种人类癌症的用途。特别关注了其作用的分子机制及其不良副作用。

相似文献

[1]
Cisplatin in cancer therapy: molecular mechanisms of action.

Eur J Pharmacol. 2014-10-5

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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Cancer Treat Rev. 2014-10-18

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[3]
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[4]
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[5]
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[6]
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[7]
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Cancer Genomics Proteomics. 2025

[8]
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[9]
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[10]
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本文引用的文献

[1]
Hydrolysis of the Anticancer Drug Cisplatin:  Pitfalls in the Interpretation of Quantum Chemical Calculations.

J Chem Theory Comput. 2006-1

[2]
Downregulation of HIPK2 increases resistance of bladder cancer cell to cisplatin by regulating Wip1.

PLoS One. 2014-5-20

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Sci Prog. 2014

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J Biol Chem. 2014-6-13

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Br J Cancer. 2014-5-1

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Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway.

Asian Pac J Cancer Prev. 2014

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Tumour Biol. 2014-7

[8]
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Tumour Biol. 2014-7

[9]
Acquisition of epithelial-mesenchymal transition phenotype and cancer stem cell-like properties in cisplatin-resistant lung cancer cells through AKT/β-catenin/Snail signaling pathway.

Eur J Pharmacol. 2013-12-12

[10]
Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway.

Am J Respir Cell Mol Biol. 2013-8

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