A novel peptide–drug conjugate GV-K for anti-colorectal cancer therapy via mitochondrial apoptosis
- 1Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China
- 2The First Department of Medical Oncology, Fourth Affiliated Hospital, China Medical University, Shenyang 110084, China
Abstract
Colorectal cancer (CRC) has the second-highest mortality rate, seriously threatening human health. Despite many advances in the field of CRC therapy, an effective cure is yet to be found. As a more potent alternative to the conventional small-molecule anti-cancer drugs, peptide-drug conjugates (PDCs) have emerged as a new class of anticancer agents. Based on the principle of drug target co-screening, our study identified a novel CRC affinity peptide, GV12, which specifically bound to the protein ANXA2 on CRC cells using phage display technology. Moreover, the peptide GV12 was capable of penetrating CRC cells but without exerting cytotoxic effects. We constructed a peptide-drug conjugate, designated GV-K, composed of GV12 and the pro-apoptotic peptide D-(KLA)2, which demonstrated significant anti-CRC effects both in vitro and in vivo. GV-K targeted the membrane protein ANXA2 and primarily internalized into CRC cells via receptor-mediated endocytosis. Subsequently, GV-K was successfully localized to the mitochondria and thereby induced apoptosis of CRC cells by triggering the cytochrome C-Apaf-1-Caspase signaling pathway. These findings reveal a novel PDC, GV-K, which targets the membrane protein ANXA2 to internalize and induce apoptosis in CRC cells, suggesting a promising strategy for targeted therapy of CRC.
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BibTeX
@article{yu2026novel,
title = {{A novel peptide–drug conjugate GV-K for anti-colorectal cancer therapy via mitochondrial apoptosis}},
author = {Lifeng Yu and Ying He and Guojia Liu and Qian Wei and Ruili Wang and Tongjie Wen and Jingqiu Chen and Qing Gao and Weitao Wang and Hualin Bai and Yan Wang and Chen Fu and Zhaojin Yu and Lin Zhao and Minjie Wei},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jul,
doi = {10.1016/j.apsb.2026.06.055},
url = {https://europepmc.org/article/PMC/PMC13729533},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A novel peptide–drug conjugate GV-K for anti-colorectal cancer therapy via mitochondrial apoptosis
AU - Lifeng Yu
AU - Ying He
AU - Guojia Liu
AU - Qian Wei
AU - Ruili Wang
AU - Tongjie Wen
AU - Jingqiu Chen
AU - Qing Gao
AU - Weitao Wang
AU - Hualin Bai
AU - Yan Wang
AU - Chen Fu
AU - Zhaojin Yu
AU - Lin Zhao
AU - Minjie Wei
PY - 2026
DA - 2026/07/01
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.06.055
UR - https://europepmc.org/article/PMC/PMC13729533
AB - Colorectal cancer (CRC) has the second-highest mortality rate, seriously threatening human health. Despite many advances in the field of CRC therapy, an effective cure is yet to be found. As a more potent alternative to the conventional small-molecule anti-cancer drugs, peptide-drug conjugates (PDCs) have emerged as a new class of anticancer agents. Based on the principle of drug target co-screening, our study identified a novel CRC affinity peptide, GV12, which specifically bound to the protein ANXA2 on CRC cells using phage display technology. Moreover, the peptide GV12 was capable of penetrating CRC cells but without exerting cytotoxic effects. We constructed a peptide-drug conjugate, designated GV-K, composed of GV12 and the pro-apoptotic peptide D-(KLA)2, which demonstrated significant anti-CRC effects both in vitro and in vivo. GV-K targeted the membrane protein ANXA2 and primarily internalized into CRC cells via receptor-mediated endocytosis. Subsequently, GV-K was successfully localized to the mitochondria and thereby induced apoptosis of CRC cells by triggering the cytochrome C-Apaf-1-Caspase signaling pathway. These findings reveal a novel PDC, GV-K, which targets the membrane protein ANXA2 to internalize and induce apoptosis in CRC cells, suggesting a promising strategy for targeted therapy of CRC.
SN - 2211-3835
SN - 2211-3843
ER -