Research Paper Volume 14, Issue 21 pp 8688—8699
Efficacy of zinc carnosine in the treatment of colorectal cancer and its potential in combination with immunotherapy in vivo
- 1 Center for Healthy Ageing and Wellness, Faculty of Health Sciences, University Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
- 2 Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing 210000, Jiangsu, China
- 3 General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China
- 4 Biocompatibility Laboratory, Centre for Research and Instrumentation, University Kebangsaan Malaysia, UKM Bangi, Bangi 43600, Selangor Darul Ehsan, Malaysia
Received: June 24, 2022 Accepted: October 31, 2022 Published: November 14, 2022
https://doi.org/10.18632/aging.204380How to Cite
Copyright: © 2022 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: A complex of Zn and carnosine, called Zinc-L-carnosine (ZnC), enjoys a wide application as part of a Zn supplement therapeutic method as well as in treating peptic ulcers. However, researches fail to confirm the biological functions possessed by ZnC as well as tumor immune microenvironment in colorectal cancer (CRC).
Methods: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model.
Results: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC.
Conclusions: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.