The interaction of berberine with chemodrugs on Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma

Abstract

Chemodrugs such as cisplatin and suberoylanilide hydroxamic acid (SAHA) are widely known for their ability to suppress Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) growth by inducing cell-cycle arrest and EBV lytic reactivation respectively. Our previous study has reported that berberine, a pure compound from Chinese medical herbs, can strongly suppress the activation of STAT3 and tumor growth of NPC cells. In this study, we aim to investigate the potential risks or benefits of taking berberine as an adjuvant agent in combination with chemodrugs. We found that berberine sensitized the cells for the cytotoxicity effects of cisplatin and SAHA, although it interfered with the cisplatin-induced G1 arrest and downregulated SAHA-induced lytic reactivation. In the in vivo experiments, the tumor growth in nude mice could be suppressed by cisplatin, SAHA or berberine treatment alone. While concurrent use of cisplatin and berberine could further suppress the tumor growth, this combined treatment was detrimental to the healthiness of mice. When the mice were treated with berberine + SAHA, the tumor nodules were swelled up with watery tumour masses. RNAscope of EBV lytic genes (e.g. BZLF1 and gp350) showed that around 10% of cells underwent lytic reactivation. Moreover, H&E staining of the tumor masses suggested the tumors cells were induced into differentiation after treating with berberine + SAHA. Inhibition of STAT3 has suggested to modulate cellular differentiation status for enhancing the cytotoxicity effects of cisplatin and SAHA. Future experiments will be performed to understand the berberine-mediated suppression of STAT3 in affecting the chemodrugs’ efficacy.