Capecitabine Regulates HSP90AB1 Expression and Induces Apoptosis via Akt/SMARCC1/AP-1/ROS Axis in T Cells

Author:

Zhang Sai12ORCID,Fan Shunli3ORCID,Wang Zhenglu24ORCID,Hou Wen5ORCID,Liu Tao5ORCID,Yoshida Sei6ORCID,Yang Shuang6ORCID,Zheng Hong2467ORCID,Shen Zhongyang24567ORCID

Affiliation:

1. School of Medicine, Nankai University, Tianjin, China

2. Organ Transplant Department, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China

3. First Central Clinical Institute, Tianjin Medical University, Tianjin, China

4. Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin First Central Hospital, Tianjin, China

5. National Health Commission’s Key Laboratory for Critical Care Medicine, Tianjin, China

6. Research Institute of Transplant Medicine, Nankai University, Tianjin, China

7. Tianjin Key Laboratory for Organ Transplantation, Tianjin, China

Abstract

Transplant oncology is a newly emerging discipline integrating oncology, transplant medicine, and surgery and has brought malignancy treatment into a new era via transplantation. In this context, obtaining a drug with both immunosuppressive and antitumor effects can take into account the dual needs of preventing both transplant rejection and tumor recurrence in liver transplantation patients with malignancies. Capecitabine (CAP), a classic antitumor drug, has been shown to induce reactive oxygen species (ROS) production and apoptosis in tumor cells. Meanwhile, we have demonstrated that CAP can induce ROS production and apoptosis in T cells to exert immunosuppressive effects, but its underlying molecular mechanism is still unclear. In this study, metronomic doses of CAP were administered to normal mice by gavage, and the spleen was selected for quantitative proteomic and phosphoproteomic analysis. The results showed that CAP significantly reduced the expression of HSP90AB1 and SMARCC1 in the spleen. It was subsequently confirmed that CAP also significantly reduced the expression of HSP90AB1 and SMARCC1 and increased ROS and apoptosis levels in T cells. The results of in vitro experiments showed that HSP90AB1 knockdown resulted in a significant decrease in p-Akt, SMARCC1, p-c-Fos, and p-c-Jun expression levels and a significant increase in ROS and apoptosis levels. HSP90AB1 overexpression significantly inhibited CAP-induced T cell apoptosis by increasing the p-Akt, SMARCC1, p-c-Fos, and p-c-Jun expression levels and reducing the ROS level. In conclusion, HSP90AB1 is a key target of CAP-induced T cell apoptosis via Akt/SMARCC1/AP-1/ROS axis, which provides a novel understanding of CAP-induced T cell apoptosis and lays the experimental foundation for further exploring CAP as an immunosuppressant with antitumor effects to optimize the medication regimen for transplantation patients.

Funder

Youth Science Fund of the Nature Science Foundation of Tianjin

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3