Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling.
Int J Oncol
; 47(6): 2173-80, 2015 Dec.
Article
in En
| MEDLINE
| ID: mdl-26499922
ABSTRACT
We investigated the mechanisms of the inhibitory effect of carbonyl reductase 1 (CR1) on ovarian cancer growth mediated by the activation of the tumor necrotic factor receptor (TNFR) pathway. OVCAR-3 and TOV21G cells overexpressing CR1 were constructed by transfecting them with CR1 cDNA by lipofection. CR1-overexpressing and control OVCAR-3 and TOV21G cells were injected subcutaneously into nude mice and the tumor growth was compared between the two groups for 3-4 weeks. The expression of TNFR1 and TNFR2 in tumors was examined immunohistochemically at the end of the experiment. Expression levels of caspase-8 and -3 activated by TNFR1, c-Jun activated by TNFR2, and NF-κB activated by both TNFR1 and TNFR2 were determined using immunohistochemistry and western blot analysis. Tumor growth was significantly suppressed in mice injected with CR1-overexpressing cells. Tumor volume in the CR1 induction group decreased temporarily until 2 weeks. Tumor cell membranes in both CR1 induction and control groups were positive for TNFR1 expression; however, total protein levels did not differ between the two groups. TNFR-2 expression was comparatively weak in both groups. The expression of NF-κB and c-Jun was weaker in the CR1 induction group than in control. In contrast, caspase-8 and -3 expression was higher in the CR1 induction group. Furthermore, the number of apoptotic cells was significantly greater in tumors that appeared after injections of both types of CR1-overexpressing cells than in those of control cancer cells. These results suggest that CR1 induces apoptosis by activating the caspase pathway via binding to TNFR1.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Signal Transduction
/
Receptors, Tumor Necrosis Factor
/
Alcohol Oxidoreductases
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Int J Oncol
Journal subject:
NEOPLASIAS
Year:
2015
Type:
Article
Affiliation country:
Japan