Taxol-Resistant Gene 1 (Txr1) Mediates Oxaliplatin Resistance by Inducing Autophagy in Human Nasopharyngeal Carcinoma Cells

Abstract

BackgroundOxaliplatin (L-OHP) is an important chemotherapy regimen for nasopharyngeal carcinoma (NPC), but can fail due to drug resistance. In this study, the role of Txr1 (taxol-resistant gene 1) in oxaliplatin resistance was investigated.Material/MethodsCell viability assay was carried out using the CellTiter-Glo Luminescent Cell Viability Assay Kit. CNE1 and CNE2 cells were cultured continuously with gradually increasing concentrations of L-OHP for 6 months to establish drug-resistant cell lines. Autophagy was detected by electron microscopy. Txr1 expression in NPC cells was detected via Western blotting and real-time quantitative PCR (qRT-PCR).ResultsIn L-OHP-resistant CNE1/L-OHP and CNE2/L-OHP cells, mRNA and protein expression of Txr1 increased compared to the parental cells, and downregulation of Txr1 re-sensitized drug-resistant cells to L-OHP. Moreover, we found that Txr1-mediated L-OHP resistance was associated with increased autophagy. Txr1-overexpression cells developed L-OHP resistance and a high level of autophagy. Inhibiting autophagy using 2 different methods – inhibition of autophagy-related gene expression and autophagy inhibitor – attenuated L-OHP resistance of NPC cells.ConclusionsWe conclude that the detection of Txr1 might become a good indicator to evaluate the treatment and prognosis of nasopharyngeal carcinoma. Our data suggest that further investigation of Txr1 in the setting of L-OHP resistance is warranted.

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

“…The most recent study on oxaliplatin resistance was carried out using head and neck carcinoma cells, CNE1 and CNE2. Chi et al suggested that Taxol-resistant gene 1 (Txr1) is a causative factor for oxaliplatin resistance [ 168 ]. They found that the mRNA and protein expression of Txr1 was increased in oxaliplatin-resistant CNE1 and CNE2 cells compared to that in the parental cells, and the cause of Txr1-mediated resistance was associated with increased autophagy [ 169 ].…”

Dexamethasone Improves the Responsiveness of Hepatoma Cells for Both Free and Solvent Containing Paclitaxel in Vitro

“…Some investigators have regarded Txr1 expression as an independent prognostic factor (Bai et al, 2010; Du et al, 2012). Also, other studies have demonstrated the mechanistic association between Txr1 gene expression and autophagy (Chi et al, 2019). Taken together, it is imperative to investigate both the cytotoxic potential of anticancer drugs and the associated regulation of genes deeply involved in their resistance and metabolism.…”

“…The upregulation of the multidrug resistance gene (MDR1) to taxans (reported in other studies) which acts as a substrate of P-glycoprotein, led to its pumping out of the cell (Miyoshi et al, 2005). This triggered the notion of using the expression of Txr1 as an indicator to evaluate the potential treatment and prognosis (Chi et al, 2019). Other intervening factor that greatly modulates the performance of drugs is represented by the xenobiotic metabolizing machinery in liver, especially cytochromes (CYPs).…”