Decreased expression of carbonyl reductase 1 promotes ovarian cancer growth and proliferation

YUKI OSAWA, YOSHIHITO YOKOYAMA, TATSUHIKO SHIGETO, MASAYUKI FUTAGAMI, HIDEKI MIZUNUMA
2014 International Journal of Oncology  
carbonyl reductase 1 (cBr1) expression level is related to tumor progression. Decreased cBr1 expression is associated with poor prognosis in ovarian cancer. We investigated the relationship between cBr1 expression level and malignant potential of ovarian cancer. oVcar-3 cells overexpressing cBr1 or knocked down for cBr1 were obtained by transfecting cBr1 plasmid Dna (pDna) or small interfering rna (sirna) by electroporation. In vitro cell proliferation and invasion were compared between the two
more » ... red between the two cell types. Subcutaneous cBr1-overexpressed oVcar-3 cells (n=10) and wild-type ones (n=5) were injected into nude mice. the cBr1 sirna was then injected twice a week into five of the 10 CBR1-overexpressed OVCAR-3 tumors. Tumor growth and metastatic behavior were observed 3 weeks after cell transplantation. cell proliferation significantly decreased in cBr1-overexpressed cells as compared to the control, whereas cell proliferation and invasion significantly increased in cBr1-suppressed cells as compared to the control. the size of the cBr1 sirna-injected tumors (n=5) increased significantly as compared to the other two groups (n=5 for each group). the number of metastatic foci in the lungs was significantly higher in mice injected with cBr1 sirna (7.0±2.0) compared to cBr1-overexpressed and wild-type tumors (0 and 2.0±2.0, respectively). Western blot analysis showed that, while vascular endothelial growth factor (Vegf)-c expression was stable in the cBr1-sirna-injected tumors, e-cadherin expression was decreased, whereas matrix metalloproteinase (MMP)-9 was increased in cBr1-sirna-injected tumors compared to the other two groups. these results showed that cBr1 decreases promoted tumor proliferation and growth as well as invasion and metastasis, suggesting that cBr1 has potential to become a new candidate for molecular targeting therapy.
doi:10.3892/ijo.2014.2810 pmid:25572536 fatcat:6qdk57j5ybek3kzearhf4bv4wu