Tamoxifen induced cardiac damage via the IL-6/p-STAT3/PGC-1α pathway.

Autor: Meng T; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China., Zhang D; Jinan Central Hospital, Jinan, Shandong, China., Zhang Y; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, Jinan, Shandong, China., Tian P; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, Jinan, Shandong, China., Chen J; Research Center of Translational Medicine, Jinan Central Hospital, Weifang Medical University, Weifang, China., Liu A; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China., Li Y; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China., Song C; Laboratory Animal Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China., Zheng Y; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, Jinan, Shandong, China. Electronic address: 8793822@qq.com., Su G; Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. Electronic address: gttstg@163.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Dec; Vol. 125 (Pt A), pp. 110978. Date of Electronic Publication: 2023 Nov 03.
DOI: 10.1016/j.intimp.2023.110978
Abstrakt: Tamoxifen (TAM) is an effective anticancer drug for breast and ovarian cancer. However, increased risk of cardiotoxicity is a long-term clinical problem associated with TAM, while the underlying mechanisms remain unclear. Here, we performed experiments in cardiomyocytes and tumor-bearing or nontumor-bearing mice, and demonstrated that TAM induced cardiac injury via the IL-6/p-STAT3/PGC-1α/IL-6 feedback loop, which is responsible for reactive oxygen species (ROS) accumulation. Compared with non-tumor bearing mice, tumor-bearing mice showed stronger cardiac toxicity after TAM injection, although there was no significant difference. In vitro experiments demonstrated STAT3 phosphorylation inhibitor can increase PGC-1α expression and protect cardiomyocyte via decreasing ROS. Since tumor has higher STAT3 phosphorylation and IL-6 expression level, our research results indicated combining TAM and STAT3 inhibitor might be an effective treatment strategy which can provide both tumor killing and cardioprotective function. Further in vivo research is needed to fully elucidate the effect and mechanisms of the combination therapy of TAM and STAT3 inhibitor.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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