Identification of PTPN1 as the anticancer target of resveratrol against Epstein-Barr virus-associated cancers

Background Epstein-Barr virus (EBV) is a well-known oncogenic virus, which plays a pivotal role in cancer chemotherapy resistance. Resveratrol has been shown to exert significant cytotoxic effects on cancer cells and enhances chemotherapy sensitivity. Nevertheless, the extensive therapeutic targets and underlying mechanisms are not well-established. Methods The efficacy of resveratrol was assessed through cellular experiments and nude mice of EBV-positive nasopharyngeal carcinoma and gastric carcinoma cells. The prediction of resveratrol’ s target genes involved the application of chemical similarity searches and molecular docking techniques. Expression data of these target genes, along with clinical data from tumor patients, were obtained from the GEO database and the TCGA database. The predictive value of models was evaluated using the Kaplan-Meier survival. Univariate and multivariate Cox regression analyses were used to examine the relationship between the target gene and prognosis. Results We observed that resveratrol can significantly inhibit cell viability and tumorigenicity in the nude mice of EBV-positive nasopharyngeal carcinoma and gastric carcinoma cells. To investigate the underlying mechanisms, we pursued a target prediction study by employing a combination of chemical similarity search and molecular docking techniques. The results suggest that resveratrol may hone in on PTPN1 as a target. PTPN1, recognized as a non-receptor protein tyrosine phosphatase, is an emerging oncogene, which is highly expressed in EBV-positive cancer cells. We proved that resveratrol engages with PTPN1 and decreases the protein stability of PTPN1. Furthermore, resveratrol can enhance the cytotoxicity of cisplatin to EBV-positive cancer cells. Conclusions Overall, our findings illuminate the anti-cancer effect of resveratrol by targeting PTPN1. We propose that resveratrol merits additional investigation as a potential anti-cancer agent for cancer therapy.