Open Access

ARTICLE

Exploring the correlation and mechanism of natural killer cell cytotoxic sensitivity against gastric cancer

WENZHUO YANG^1,#, HAODONG CHEN^2,#, ZHILAN ZHANG³, ZHIYONG XIA³, YUANYUAN JIN^1,*, ZHAOYONG YANG^1,*

1 The Department of Oncology, Beijing Hospital, Beijing, 100034, China
2 NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, 100050, China
3 The School of Pharmacy, North China University of Science and Technology, Tangshan, 063210, China

* Corresponding Authors: YUANYUAN JIN. Email: ; ZHAOYONG YANG. Email:
# These two authors contributed equally to this work

Oncology Research 2025, 33(6), 1485-1494. https://doi.org/10.32604/or.2025.059426

Received 08 October 2024; Accepted 24 January 2025; Issue published 29 May 2025

Abstract

Background: Human natural killer (NK) cells have attracted widespread attention as a potential adoptive cell therapy (ACT). However, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. There is an urgent need to explore a suitable new treatment plan to overcome weaknesses and support the superior therapeutic activity of NK cells. Methods: In this study, the mechanisms underlying the susceptibility of gastric cancer (GC) cell lines AGS, HGC-27, and NCI-N87 to NK cell-mediated cytotoxicity were explored. Results: Lactic dehydrogenase (LDH) release assays showed that all three GC cell lines were susceptible to the umbilical cord blood NK (UCB-NK) cells, and HGC-27 cells with high CD56 expression were the most sensitive to UCB-NK, followed by NCI-N87 and AGS. When the expression of CD56 in HGC-27 cells decreased, the lytic activity of NK cells in HGC-27 cells was abating. In addition, combining oxaliplatin with NK cells produced additive anti-tumor effects in vitro, which may have resulted from oxaliplatin-induced NK group 2 member D (NKG2DL) upregulation in GC cells. These results of cytotoxicity activity showed that inhibition of CD56 expression might suppress the sensitivity of GC cells to NK cell-mediated cytotoxicity, and upregulation of the expression of NKG2DL on the surface of GC cells by oxaliplatin could enhance the killing sensitivity of NK cells. Conclusion: Collectively, our study provides a deeper theoretical foundation and a better therapeutic strategy for NK cell immunotherapy in the treatment of human GC.

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Supplementary Material

Supplementary Material File

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