WNT3 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating the Canonical ß-catenin Pathway
Oral squamous cell carcinoma (OSCC) represents a major malignancy in the oral and maxillofacial region. The primary therapeutic agents, 5-fluorouracil (5FU) and oxaliplatin (OXA), often encounter the challenge of chemoresistance, leading to treatment failure. The WNT/ß-catenin signaling pathway, closely tied with chemoresistance, offers a promising therapeutic avenue. This study delves into this potential connection. 5FU-resistant and OXA-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells were analyzed by RNA sequencing analysis, which was then substantiated via RT-qPCR and western blot. The influence of the WNT signaling on OSCC drug resistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor, MSAB, was probed for its capacity to boost the efficacy of 5FU or OXA. Through transcriptome sequencing, successfully derived 5FU-resistant and OXA-resistant cell lines revealed a conspicuous activation of the WNT/ß-catenin signaling pathway in the drug-resistant cells. WNT3 was identified as a pivotal factor contributing to chemoresistance in OSCC. Counteracting ß-catenin notably augmented the therapeutic potency of 5FU and OXA. Our study underscored the activation of the WNT/ß-catenin signaling pathway in resistant OSCC cell lines. By modulating WNT signaling activity, drug resistance in OSCC cells may be effectively circumvented. Overall design: To elucidate the chemoresistance mechanism, we established 5FU-resistant and OXA-resistant cells. We extracted RNA and employed RNA-seq to identify key differentially expressed genes between parental and resistant cells.