Noxa Enhances the Cytotoxic Effect of Gemcitabine in Human Ovarian Cancer Cells
Noxa Enhances the Cytotoxic Effect of Gemcitabine in Human Ovarian Cancer Cells
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Noxa 增强吉西他滨对人卵巢癌细胞的细胞毒性作用
DOI：
10.1089/cbr.2011.1126
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发表时间：
2012-05-01
影响因子：
3.4
通讯作者：
Li, Ming-yuan
中科院分区：
文献类型：
--
作者：
Cao, Kang;Yang, Jing;Li, Ming-yuan
Noxa是细胞凋亡内在通路中重要的促凋亡蛋白。因此，我们通过实验研究Noxa是否能增强吉西他滨对人卵巢癌细胞株（A2780和COC1）的细胞毒作用。在本研究中，通过MTT实验、Hoechst染色和流式细胞术分析证实，诺沙联合吉西他滨在体外显著抑制了A2780和COC1细胞的增殖。此外，Noxa与吉西他滨联合用药可抑制肿瘤生长，延长裸鼠体内生存期。免疫组织化学抗pcna染色和tdt介导的dutp -生物素镍端标记（TUNEL）实验显示，联合治疗还通过抑制增殖和诱导细胞凋亡来抑制肿瘤异种移植物的生长。我们的数据表明，Noxa对人卵巢癌细胞具有强大的促凋亡活性，并且与单独使用这两种药物相比，Noxa和吉西他滨联合使用对卵巢癌细胞具有更显著的细胞毒作用。据我们所知，我们已经提供了Noxa可以增强卵巢癌细胞对吉西他滨的治疗反应的第一个证据，并且它可能是卵巢癌治疗中潜在的化学增敏剂。
Noxa is an important proapoptotic protein in the intrinsic pathway of cell apoptosis. Experiments were carried out to investigate whether Noxa could, therefore, enhance the cytotoxic effect of gemcitabine in human ovarian cancer cell lines (A2780 and COC1). In this study, the combined treatment of Noxa and gemcitabine, in vitro, significantly inhibited the proliferation of A2780 and COC1 cells, as verified by MTT assay, Hoechst staining, and flow cytometric analysis. Moreover, the combination of Noxa and gemcitabine inhibited tumor growth and prolonged the survival of nude mice in vivo. The combined treatment also inhibited the growth of tumor xenografts through the inhibition of proliferation and the induction of apoptosis, as observed in immunohistochemical anti-PCNA staining and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Our data suggest that Noxa exhibited potent proapoptotic activity against human ovarian cancer cells, and the combination of Noxa and gemcitabine showed a more significant cytotoxic effect against ovarian cancer cells in comparison with either of these agents alone. To our knowledge, we have provided the first evidence that Noxa can enhance therapeutic responses of ovarian cancer cells to gemcitabine, and that it could be potentially useful as a chemosensitizer in ovarian cancer therapy.