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作者

Jinghua Chen, Jie Liu, Xiaolin Liu, Jun Wang, Xiumei Wang, Xin Ye, Qi Xie, Jing Liang, Yan Li

作者单位

com. ⁸ Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Oncology, Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. liyan16766@16 com. ⁷ Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China. liyan16766@16 com. Affiliations ¹ Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China. ² Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Oncology, Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. ³ Department of Pediatric Intensive Care Unit, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China. ⁴ Department of Oncology, The Yuncheng Chenxin Hospital, Heze, China. ⁵ Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Oncology, Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. xieqi@sdfmu.edu.cn. ⁶ Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Oncology, Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. liangjing0531@16

刊名

Molecular biology reports

年份

2024

卷号

Vol.51 No.1

页码

86

ISSN

1573-4978

关键词

Colorectal cancer Hsp70 PD-1 blockade Shikonin Stable microsatellites.

摘要

Background: PD-1 blockade has shown impressive clinical outcomes in colorectal cancers patients with high microsatellite instability . However, the majority of patients with colorectal cancer who present low microsatellite instability or stable microsatellites show little response to PD-1 blockade therapy. Here, we have demonstrated that Shikonin could induce cell death of CT26 cells via classically programmed and immunogenic pathways. Methods and results: SK promoted the membrane exposure of...更多

Background: PD-1 blockade has shown impressive clinical outcomes in colorectal cancers patients with high microsatellite instability . However, the majority of patients with colorectal cancer who present low microsatellite instability or stable microsatellites show little response to PD-1 blockade therapy. Here, we have demonstrated that Shikonin could induce cell death of CT26 cells via classically programmed and immunogenic pathways. Methods and results: SK promoted the membrane exposure of calreticulin and upregulated the expression of heat shock protein 70 . The upregulation of Hsp70 was dependent on ROS induced by SK and silencing of PKM2 in CT26 cells reverts ROS upregulation. Besides, SK synergizes with PD-1 blockade in CT26 tumor mice model, with the increase of intramural DC cells and CD8T cells. The expression of Hsp70 in tumor tissue was also increased in combinational SK plus αPD-1 therapy group. Conclusions: Our study elucidated the potential role of 'Shikonin-PKM2-ROS-Hsp70' axis in the promotion of efficacy of PD-1 blockade in CRC treatments, providing a potential strategy and targets for improving the efficacy of PD-1 blockade in colorectal cancer.收起

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