Decreased expression of carbonyl reductase 1 promotes ovarian cancer growth and proliferation
Decreased expression of carbonyl reductase 1 promotes ovarian cancer growth and proliferation
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DOI：
10.3892/ijo.2014.2810
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发表时间：
2015-03-01
影响因子：
5.2
通讯作者：
Mizunuma, Hideki
中科院分区：
文献类型：
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作者：
Osawa, Yuki;Yokoyama, Yoshihito;Mizunuma, Hideki
羰基还原酶 1 (CBR1) 表达水平与肿瘤进展相关。 CBR1 表达降低与卵巢癌预后不良相关。我们研究了CBR1表达水平与卵巢癌恶性潜能之间的关系。通过电穿孔转染 CBR1 质粒 DNA (pDNA) 或小干扰 RNA (siRNA) 获得过表达 CBR1 或 CBR1 敲低的 OVCAR-3 细胞。比较两种细胞类型之间的体外细胞增殖和侵袭。将过表达CBR1的OVCAR-3细胞(n=10)和野生型细胞(n=5)皮下注射到裸鼠体内。然后每周两次将 CBR1 siRNA 注射到 10 个 CBR1 过表达 OVCAR-3 肿瘤中的 5 个肿瘤中。细胞移植后3周观察肿瘤生长和转移行为。与对照相比，CBR1过表达的细胞的细胞增殖显着降低，而与对照相比，CBR1抑制的细胞的细胞增殖和侵袭显着增加。与其他两组（每组 n=5）相比，注射 CBR1 siRNA 的肿瘤（n=5）的大小显着增加。与 CBR1 过表达肿瘤和野生型肿瘤（分别为 0 和 2.0 +/- 2.0）相比，注射 CBR1 siRNA 的小鼠肺部转移灶的数量（7.0 +/- 2.0）显着更高。 Western blot分析显示，与其他两组相比，注射CBR1-siRNA的肿瘤中血管内皮生长因子（VEGF）-C表达稳定，但E-钙粘蛋白表达降低，而基质金属蛋白酶（MMP）-9在注射CBR1-siRNA的肿瘤中增加。这些结果表明CBR1的减少促进了肿瘤的增殖和生长以及侵袭和转移，这表明CBR1有潜力成为分子靶向治疗的新候选者。
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 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.