CD44v-dependent upregulation of xCT is involved in the acquisition of cisplatin-resistance in human lung cancer A549â¯cells.
Biochem Biophys Res Commun
; 507(1-4): 426-432, 2018 12 09.
Article
em En
| MEDLINE
| ID: mdl-30448176
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 ACR20â¯cells, by stepwise increasing CDDP concentrations up to 4 and 20⯵M, respectively. ACR4 and ACR20â¯cells showed 6- and 16-fold higher resistance to CDDP than A549â¯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 ACR20â¯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 ACR20â¯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 ACR20â¯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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Cisplatino
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Resistencia a Medicamentos Antineoplásicos
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Receptores de Hialuronatos
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Sistema y/ de Transporte de Aminoácidos
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article