C-reactive protein promotes tongue squamous cell carcinoma chemoresistance by inhibiting the activation of caspase-3/9 via the CD64/AKT/mTOR pathway.

Recent studies have shown that C-reactive protein (CRP) participates in multiple types of cancer development. Here, the aim of this study was to investigate the role of CRP in tongue squamous cell carcinoma (TSCC) chemoresistance. Immunohistochemical staining showed that CRP expression was upregulated in TSCC tissues from cisplatin-resistant patients compared with that in cisplatin-sensitive TSCC samples. The CRP expression level was positively correlated with that of the drug-resistant marker MDR1. Moreover, functional experiments showed that CRP increased cell viability and decreased cisplatin-induced apoptosis. CRP also increased the expression levels of MDR1 and Bcl-2 and decreased the expression level of Bax. Furthermore, CRP decreased the activity of caspase-3. Mechanistically, CRP could bind to Fcgamma receptor I (FcgammaRI, also known as CD64) and activate the AKT/mTOR pathway to inhibit the activation of caspase-3/9, as shown by co-immunoprecipitation (Co-IP) assay and western blotting assays. In addition, CRP promoted tumour growth and decreased cleaved caspase-3/9 expression in BALB/c nude mice. Taken together, our findings indicate that CRP promotes TSCC chemoresistance by inhibiting the activation of caspase-3/9 via the FcgammaRI/AKT/mTOR pathway. Thus, CRP could potentially be considered as a therapeutic target for reducing TSCC chemoresistance.