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 Fcγ receptor I (FcγRI, 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 FcγRI/AKT/mTOR pathway. Thus, CRP could potentially be considered as a therapeutic target for reducing TSCC chemoresistance.

最近的研究表明，C 反应蛋白（CRP）参与多种类型的癌症发展。本研究的目的是探讨 CRP 在舌鳞状细胞癌 (TSCC) 化疗耐药中的作用。免疫组织化学染色显示，与顺铂敏感的TSCC样本相比，顺铂耐药患者的TSCC组织中CRP表达上调。 CRP表达水平与耐药标志物MDR1的表达水平呈正相关。此外，功能实验表明，CRP 可以增加细胞活力并减少顺铂诱导的细胞凋亡。 CRP还增加MDR1和Bcl-2的表达水平并降低Bax的表达水平。此外，CRP 降低了 caspase-3 的活性。免疫共沉淀（Co-IP）检测和蛋白质印迹显示，从机制上讲，CRP可以与Fcγ受体I（FcγRI，也称为CD64）结合并激活AKT/mTOR通路，从而抑制caspase-3/9的激活化验。此外，CRP 促进 BALB/c 裸鼠中的肿瘤生长并降低 caspase-3/9 的表达。综上所述，我们的研究结果表明，CRP 通过 FcγRI/AKT/mTOR 途径抑制 caspase-3/9 的激活，从而促进 TSCC 化疗耐药。因此，CRP 可能被视为减少 TSCC 化疗耐药性的治疗靶点。