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多柔比星、间充质干细胞毒性和抗肿瘤活性:对临床应用的影响。

Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use.

机构信息

School of Pharmacy and Biomedical Science, Curtin University, Perth, WA, Australia.

Curtin Health Innovation Research Institute, Perth, WA, Australia.

出版信息

J Pharm Pharmacol. 2018 Mar;70(3):320-327. doi: 10.1111/jphp.12869. Epub 2018 Jan 22.

Abstract

OBJECTIVES

The use of doxorubicin, an antineoplastic medication used for the treatment of cancers via mechanisms that prevent replication of cells or lead to their death, can result in damage to healthy cells as well as malignant. Among the affected cells are mesenchymal stem cells (MSCs), which are involved in the maintenance and repair of tissues in the body. This review explores the mechanisms of biological effects and damage attributed to doxorubicin on MSCs. The PubMed database was used as a source of literature for this review.

KEY FINDINGS

Doxorubicin has the potential to lead to significant and irreversible damage to the human bone marrow environment, including MSCs. The primary known mechanism of these changes is through free radical damage and activation of apoptotic pathways. The presence of MSCs in culture or in vivo appears to either suppress or promote tumour growth. Interactions between doxorubicin and MSCs have the potential to increase chemotherapy resistance.

SUMMARY

Doxorubicin-induced damage to MSCs is of concern clinically. However, MSCs also have been associated with resistance of tumour cells to drugs including doxorubicin. Further studies, particularly in vivo, are needed to provide consistent results of how the doxorubicin-induced changes to MSCs affect treatment and patient health.

摘要

目的

多柔比星是一种用于治疗癌症的抗肿瘤药物,其作用机制是阻止细胞复制或导致细胞死亡,因此可能会对健康细胞和恶性细胞造成损伤。间充质干细胞(MSCs)是受影响的细胞之一,其参与了体内组织的维持和修复。本综述探讨了多柔比星对 MSCs 的生物学效应和损伤的机制。本综述的文献来源是 PubMed 数据库。

主要发现

多柔比星有可能对包括 MSCs 在内的人类骨髓环境造成严重且不可逆转的损伤。这些变化的主要已知机制是通过自由基损伤和凋亡途径的激活。MSC 无论是在培养物中还是在体内存在,似乎都能抑制或促进肿瘤生长。多柔比星与 MSCs 之间的相互作用可能会增加化疗耐药性。

总结

多柔比星诱导的 MSCs 损伤在临床上受到关注。然而,MSCs 也与肿瘤细胞对包括多柔比星在内的药物的耐药性有关。需要进一步的研究,特别是在体内,以提供多柔比星诱导的 MSCs 变化如何影响治疗和患者健康的一致结果。

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