MAP2K6-FP Enhances the Sensitiveness of Paclitaxel for Ovarian Cancer via Inducing Autophagy.
Int J Gynecol Cancer
; 27(6): 1082-1087, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28604448
ABSTRACT
BACKGROUND:
Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Recent studies have revealed an association between autophagy and drug resistance.METHODS:
We previously synthesized a MAPK kinase-recombinant fusion protein, MAP2K6-FP, that contains 3 domains a protein transduction domain TAT, a human ovarian cancer HO8910 cell-specific binding peptide, and a potential antitumor effector domain MKK6(E). In this study, we investigated the effect of MAP2K6-FP on HO8910 cells treated with paclitaxel.RESULTS:
The IC50 (concentration by which 50% cell growth was inhibited) was 20 µM for paclitaxel alone, 1.5 µg/mL for MAP2K6-FP alone, and 0.3 µg/mL for MAP2K6-FP and 15 µM for paclitaxel if combined, respectively. In addition, immunohistochemistry assay demonstrated that tumor tissues from ovarian cancer patients showed higher expression of LC-3, the autophagy-related protein, compared with normal ovarian tissues. MAP2K6-FP (0, 2.5, 5, 10, 20, and 40 µg/mL) dose-dependently increased the LC-3 expression in HO8910 cells. Immunofluorescence assay showed that paclitaxel alone increased the expression of LC-3 in HO8910 cells, which was further enhanced by the combination with MAP2K6-FP. Downregulation of LC-3 expression using LC-3 small interfering RNA inhibited the cytotoxicity effect of MAP2K6-FP. Furthermore, either MAP2K6-FP alone or in combination with paclitaxel increased the ratio of expressions of Beclin-1/Bcl-2, another autophagy-related markers, compared with paclitaxel alone.CONCLUSIONS:
MAP2K6-FP enhanced the sensitiveness of paclitaxel for ovarian cancer via inducing autophagy.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Proteínas Recombinantes de Fusión
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Paclitaxel
/
MAP Quinasa Quinasa 6
Tipo de estudio:
Diagnostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Int J Gynecol Cancer
Asunto de la revista:
GINECOLOGIA
/
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
China