xCT expression modulates cisplatin resistance in Tca8113 tongue carcinoma cells

Abstract

Abstract. Tongue squamous cell carcinoma (TSCC), which is a subtype of head and neck cancer, is the most common type of oral cancer. Due to its high recurrence rate and chemoresistance, the average survival rate for patients with TSCC remains unsatisfactory. At present, cisplatin (CDDP) is utilized as the first-line treatment for numerous solid neoplasms, including TSCC. CDDP resistance develops in the majority of patients; however, the mechanism of such resistance remains unknown. Therefore, the present study aimed to clarify the mechanism of CDDP resistance and attempted to reduce chemoresistance. The results indicated that CDDP significantly increased expression of xCT, which is the light chain and functional subunit of the glutamate/cysteine transporter system x c -, and a subsequent increase in glutathione (GSH) levels was observed. The present study demonstrated that the upregulation of xCT expression and intercellular GSH levels contributed to CDDP resistance in TSCC cells. Furthermore, xCT suppression, induced by small interfering RNA or pharmacological inhibitors, sensitized TSCC cells to CDDP treatment. In conclusion, the present study revealed that CDDP-induced xCT expression promotes CDDP chemoresistance, and xCT inhibition sensitizes TSCC cells to CDDP treatment. These results provide a novel insight into the molecular mechanisms involved in TSCC cell chemoresistance.

Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

“…The synergetic anti-cancer effect of LAT inhibition was also reported in a study using gefitinib, a clinically targeted therapeutic EGFR inhibitor, to enhance cytotoxicity under stress (e.g., amino acid starvation culture condition) in HNSCC cells [131]. Several studies have also documented that the other two amino acid transporters ASCT2 and xCT mediate chemotherapy and EGFR-targeted therapy resistance in HNSCC cells after treatments of CDDP, cetuximab and AG1478 [132,133,134], implying that amino acid transporters could be a therapeutic target in patients with HNSCCs. On a molecular basis, a recent study demonstrated that xCT-mediated therapeutic resistance occurs mainly through the regulation of ferroptosis [135].…”

MiR‐375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion

“…SLC7A11 is one of the amino‐acid transporters, which plays an important role in cell metabolism . Previous studies indicated that SLC7A11 plays a key role in chemotherapy resistance . A study conducted by Zhang et al.…”

“…A study conducted by Zhang et al. reported that SLC7A11 may modulate cisplatin (CDDP) resistance and they also concluded that CDDP can elevate the expression of SLC7A11 significantly in TSCC cells (tongue carcinoma cells) which is another type of head and neck tumor . However, Zhang et al.…”

“…The expression of SLC7A11 has been detected in multiple malignant tumors and can be linked with poor prognosis and medication resistance . Apart from the potential relationship between SLC7A11 and ovarian cancer, another study discovered that the expression of SLC7A11 is able to regulate the resistance of cisplatin in patients with tongue squamous cell carcinoma which is another type of oral tumor .…”

Using weighted gene co-expression network analysis to identify key modules and hub genes in tongue squamous cell carcinoma

“…[2] According to the literature, the 5-year survival rate has not been significantly improved in recent years, which maintained unsatisfactory. [3] Therefore, the early diagnosis and treatment of TSCC patients is still a difficult problem.…”