title: xCT expression modulates cisplatin resistance in Tca8113 tongue carcinoma cells.
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 xc-, 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.
authors.affiliation: Department of Stomatology, No. 463 Hospital of Chinese PLA, Shenyang, Liaoning 110042, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, No. 463 Hospital of Chinese PLA, Shenyang, Liaoning 110042, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Stomatology, No. 463 Hospital of Chinese PLA, Shenyang, Liaoning 110042, P.R. China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Stomatology, No. 463 Hospital of Chinese PLA, Shenyang, Liaoning 110042, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Xu
authors.affiliation: Department of Stomatology, No. 463 Hospital of Chinese PLA, Shenyang, Liaoning 110042, P.R. China.
authors.forename: Xuanning
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Stomatology, No. 463 Hospital of Chinese PLA, Shenyang, Liaoning 110042, P.R. China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: DU
keywords: ATF4; Nrf2; cisplatin; sulfasalazine; tongue carcinoma cells; xCT