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CD44v-dependent upregulation of xCT is involved in the acquisition of cisplatin-resistance in human lung cancer A549 cells.
Horibe, Sayo; Kawauchi, Shoji; Tanahashi, Toshihito; Sasaki, Naoto; Mizuno, Shigeto; Rikitake, Yoshiyuki.
Afiliação
  • Horibe S; Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan. Electronic address: s-horibe@kobepharma-u.ac.jp.
  • Kawauchi S; Educational Center for Clinical Pharmacy, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan.
  • Tanahashi T; Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan; Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Sasaki N; Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan.
  • Mizuno S; Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan; Endoscopy Department, Kindai University Nara Hospital, 1248-1, Otoda-cho, Ikoma 630-0293, Japan.
  • Rikitake Y; Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan.
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 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação para Cima / Cisplatino / Resistencia a Medicamentos Antineoplásicos / Receptores de Hialuronatos / Sistema y/ de Transporte de Aminoácidos / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação para Cima / Cisplatino / Resistencia a Medicamentos Antineoplásicos / Receptores de Hialuronatos / Sistema y/ de Transporte de Aminoácidos / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article