Anti-Gastric Cancer Effect of Purified Omphalia lapidescens Protein via Regulating the JAK/STAT3 Signaling Pathway

Abstract

Gastric cancer is the leading cause of cancer-related death worldwide. The aim of present study was to investigate the anti-tumor effect of purified Omphalia lapidescens protein (pPeOp) in gastric cancer. Microarray analysis was performed to find out differentially expressed genes in pPeOp-treated MC-4 gastric cancer cells. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) three signaling pathway was most likely to be altered based on bioinformatics analysis. Interleukin-6 (IL-6) and NSC74859 were used as the agonist and inhibitor of the JAK/STAT3 signaling pathway, respectively. Flow cytometry and MTS assay were used for cell proliferation and viability analysis in pPeOp-treated gastric cancer cell lines with IL-6 or NSC74859. The anti-tumor effect was increased when pPeOp were co-treated with IL-6, while decreased in inhibitor treatment. The expression of the crucial members in the pathway of MC-4 cells, including glycoprotein 130 (GP130), JAK1, JAK2, STAT3, p-STAT3, suppressor of cytokine signaling SOCS1 and SOCS3, was detected by western blotting. pPeOp exhibited promising anticancer effect in the xenograft nude mice model, established by STAT3 knock down gastric cancer cells.Thus, JAK/STAT3 inhibition partially contributed to the anticancer effect of pPeOp, which may serve as a novel strategy for gastric cancer.

Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1960385

Acknowledgment

The authors are particularly grateful to Zhejiang Provincial Center for Disease and Prevention Centre for providing us with cells.

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

The manuscript has not been submitted other journals for publication, in whole or in part, and all the authors listed have approved the manuscript for publication. All animal experiments were conducted out in Shanghai GeneChem Corporation experimental center (rodent license SCXK(Shanghai) 2013-0018). The study was approved by the Ethics Committee of Shanghai Linchang Biotechology Corporationand and was in accordance with the Declaration of Helsinki.

Funding

Dat Availability

The datasets used or analyzed during the present study are available from the corresponding author on reasonable request. The gene expression data in our manuscript has been deposited in Gene Expression Omnibus (GEO) (accession number: GSE141914, the direct link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE141914).

Additional information

Funding

The present study was supported by grants from the National Natural Science Foundation Project (81874355) and the Zhejiang Provincial Natural Science Foundation (LY18H280008).