Your browser doesn't support javascript.
loading
MDR reversal activity of bromotetrandrine in vitro and in vivo / 中国实验血液学杂志
Journal of Experimental Hematology ; (6): 1183-1191, 2009.
Artigo em Inglês | WPRIM | ID: wpr-343322
ABSTRACT
The present study was aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM accumulation and the protein levels of P-glycoprotein (P-gp) were detected by flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of BrTet and Tet was investigated by using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No enhancement effect by BrTet was seen in K562 xenografts. It is concluded that BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR modulator for eventual assessment in the clinic.
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Membro 1 da Subfamília B de Cassetes de Ligação de ATP / Resistência a Múltiplos Medicamentos / Resistencia a Medicamentos Antineoplásicos / Subfamília B de Transportador de Cassetes de Ligação de ATP / Células K562 / Ensaios Antitumorais Modelo de Xenoenxerto / Benzilisoquinolinas / Genética / Metabolismo Limite: Animais / Feminino / Humanos Idioma: Inglês Revista: Journal of Experimental Hematology Ano de publicação: 2009 Tipo de documento: Artigo

Similares

MEDLINE

...
LILACS

LIS

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Membro 1 da Subfamília B de Cassetes de Ligação de ATP / Resistência a Múltiplos Medicamentos / Resistencia a Medicamentos Antineoplásicos / Subfamília B de Transportador de Cassetes de Ligação de ATP / Células K562 / Ensaios Antitumorais Modelo de Xenoenxerto / Benzilisoquinolinas / Genética / Metabolismo Limite: Animais / Feminino / Humanos Idioma: Inglês Revista: Journal of Experimental Hematology Ano de publicação: 2009 Tipo de documento: Artigo