Therapeutic efficacy of a new topoisomerase I and II inhibitor TAS-103, against both P-glycoprotein-expressing and -nonexpressing drug-resistant human small-cell lung cancer.
Oncol Res
; 11(5): 219-24, 1999.
Article
em En
| MEDLINE
| ID: mdl-10608616
ABSTRACT
We examined the effect of a novel topoisomerase I and II (topo I and II) inhibitor, TAS-103, on P-glycoprotein (P-gp)-expressing and -nonexpressing drug-resistant human small-cell lung cancer (SCLC) cells in vitro and in vivo. We observed that TAS-103 was effective in inhibiting in vitro proliferation of human SCLC (SBC-3 and H69) cells and their drug-resistant variants SBC-3/ADM or SBC-3/CDDP and H-69/VP, respectively. SBC-3/ADM and H-69/VP expressed high P-gp, whereas SBC-3/CDDP did not. TAS-103 also effectively reduced the tumor growth (more than 50% inhibition) of the parental as well as MDR SCLC cells grown SC in nude mice. Adriamycin (ADM) and cisplatin (CDDP), on the other hand, were effective only against the parental cells, while these drugs failed to inhibit the respective drug-resistant variants in vitro or in vivo. TAS-103 was observed to induce apoptosis dose dependently in the parental as well as drug-resistant SCLC cells as analyzed after 48 h of in vitro treatment, suggesting that the stabilization of cleavable topo I- or II-DNA complexes by topo I and II inhibitors like TAS-103 is followed by apoptosis of the cells. Overall, our study suggests that TAS-103 may have clinical application against drug-resistant human SCLC.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
4_antimicrobial_resistance
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6_other_respiratory_diseases
/
6_trachea_bronchus_lung_cancer
Assunto principal:
Carcinoma de Células Pequenas
/
Inibidores da Topoisomerase I
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Inibidores da Topoisomerase II
/
Aminoquinolinas
/
Indenos
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Neoplasias Pulmonares
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Antineoplásicos
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Oncol Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Japão