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11/17/2023 8:50:53 AM | Browse: 69 | Download: 3
Publication Name World Journal of Gastroenterology
Manuscript ID 87228
Country China
Category Medicine, Research & Experimental
Manuscript Type Basic Study
Article Title Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis
Manuscript Source Unsolicited Manuscript
All Author List Zheng-Yan Yang, Yi-Wei Zhao, Jing-Rui Xue, Ran Guo, Zhi Zhao, Han-Di Liu, Zhi-Guang Ren and Ming Shi
Funding Agency and Grant Number
Funding Agency Grant Number
Youth Fund of National Natural Science Foundation of China 81803575
Youth Fund of National Natural Science Foundation of China 31902287
Kaifeng Science and Technology Development Plan Project 2203008
College Students Innovation and Entrepreneurship Training Program of Henan University 20231022007
Key Specialized Research and Promotion Project of Henan Province in 2023 232102311205
Henan Medical Science and Technology Research Program Project LHGJ20210801
Corresponding Author Zhi-Guang Ren, Doctor, Associate Professor, Department of Pathology, School of Basic Medical Science, Henan University, No. 1 Jinming Street, Kaifeng 475004, Henan Province, China. renzhiguang66@outlook.com
Key Words Gastric cancer; Trastuzumab resistance; Thioridazine; S-phase kinase associated protein 2; Glycolysis
Core Tip S-phase kinase-interacting protein 2 (Skp2) has been shown to be a reliable prognostic indicator of unfavorable outcomes for gastric cancer (GC). However, no agents specifically targeting Skp2 have been successfully developed. In this study, we proved that thioridazine restores the sensitivity of GC cells to trastuzumab both in vivo and in vitro by inhibiting Skp2-mediated glycolysis. Furthermore, the combination of thioridazine and lapatinib exhibits enhanced inhibitory effects compared with either monotherapy on the growth and survival of trastuzumab-resistant GC cells. Overall, this study suggests the potential of a thioridazine-based therapy to overcome trastuzumab resistance in human epidermal growth factor receptor 2-positive GC by targeting Skp2.
Citation Yang ZY, Zhao YW, Xue JR, Guo R, Zhao Z, Liu HD, Ren ZG, Shi M. Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis. World J Gastroenterol 2023; 29(45): 5974-5987
Received
2023-09-17 15:07
Peer-Review Started
2023-09-17 15:08
To Make the First Decision
Return for Revision
2023-10-08 05:08
Revised
2023-10-19 12:17
Second Decision
2023-11-14 01:12
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief
2023-11-17 08:50
Articles in Press
2023-11-17 08:50
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript
2023-11-28 03:18
ISSN 1007-9327 (print) and 2219-2840 (online)
Open Access This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
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