Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine.
Anticancer Res
; 36(11): 5867-5874, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27793910
ABSTRACT
AIM:
To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells. MATERIALS ANDMETHODS:
We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU).RESULTS:
HAL and FLU co-treatment inhibited the growth and increased apoptosis via G2 arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells.CONCLUSION:
These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells.Palavras-chave
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flufenazina
/
Furanos
/
Cetonas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2016
Tipo de documento:
Article