RRC ID 55919
著者 Horibe S, Kawauchi S, Tanahashi T, Sasaki N, Mizuno S, Rikitake Y.
タイトル CD44v-dependent upregulation of xCT is involved in the acquisition of cisplatin-resistance in human lung cancer A549 cells.
ジャーナル Biochem Biophys Res Commun
Abstract Cisplatin (CDDP) is widely used as an anti-cancer platinum agent but its therapeutic efficacy is limited by acquired drug resistance. To develop a new therapeutic strategy that could overcome this resistance, it is important to characterize CDDP-resistant cancer cells. Here we established human lung cancer A549 cell-derived low- and high-grade CDDP-resistant sublines, termed ACR4 and ACR20 cells, by stepwise increasing CDDP concentrations up to 4 and 20 μM, respectively. ACR4 and ACR20 cells showed 6- and 16-fold higher resistance to CDDP than A549 cells, respectively. Cell migration, invasion, and sphere formation were significantly decreased, whereas expression of the stem cell marker CD44v was increased in order of A549, ACR4, and ACR20 cells. The expression of the cystine-glutamate transporter xCT, which is encoded by SLC7A11, was upregulated because of the increased cell surface expression of CD44v in ACR20 cells. Treatment with the xCT inhibitor salazosulfapyridine and knockdown of SLC7A11 mRNA by a specific siRNA significantly improved sensitivity to CDDP in A549, ACR4, and ACR20 cells. Thus, our results suggest that CD44v overexpression is not involved in cancer stem cell properties but increases xCT expression, which leads to the acquisition of CDDP-resistance. This mechanism may contribute to the development of a new therapeutic strategy that can overcome resistance.
巻・号 507(1-4)
ページ 426-432
公開日 2018-12-9
DOI 10.1016/j.bbrc.2018.11.055
PII S0006-291X(18)32469-0
PMID 30448176
MeSH A549 Cells Amino Acid Transport System y+ / genetics* Amino Acid Transport System y+ / metabolism Biomarkers, Tumor / metabolism Cell Membrane / drug effects Cell Membrane / metabolism Cisplatin / pharmacology* Drug Resistance, Neoplasm / drug effects* Humans Hyaluronan Receptors / metabolism* Inhibitory Concentration 50 Lung Neoplasms / genetics* Lung Neoplasms / pathology Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Pluripotent Stem Cells / drug effects Pluripotent Stem Cells / metabolism Up-Regulation* / drug effects
IF 2.705
引用数 1
リソース情報
ヒト・動物細胞 A549(RCB0098)