| 谢晓 梅举 肖海波 丁芳宝 钟竑 朱家全马南.PHD1 通过下调NF-γB 介导的cyclinD1 的表达抑制肺癌细胞的
生长和增殖[J].现代生物医学进展英文版,2014,14(11):2001-2005. |
| PHD1 通过下调NF-γB 介导的cyclinD1 的表达抑制肺癌细胞的
生长和增殖 |
| PHD1 Inhibits NF-γB Mediated CyclinD1 Expression and Proliferationof Lung Cancer Cells |
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| DOI： |
| 中文关键词: 肺癌 细胞增殖 PHD1 Cyclin NF-κB |
| 英文关键词: Lung cancer Cell proliferation PHD1 Cyclin NF-κB |
| 基金项目:国家自然科学基金项目（81071924） |
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| 中文摘要: |
| 目的：探讨PHD1 在肺癌中的功能，并进一步研究其分子机制，为肺癌的治疗寻找新的靶点。方法：选取人肺癌细胞A549，以
脂质体为载体一方面过表达PHD1，另一方面合成设计靶向PHD1 的siRNA 沉默PHD1，利用荧光素酶检测NF-γB 的活性，分别
用western blot和real-time PCR 检测cyclinD1 的表达水平。在A549细胞中过量稳定表达带GFP 标记的PHD1，流式细胞仪检测
细胞周期变化，测量细胞的生长曲线，并将细胞注射到裸鼠皮下观察其成瘤情况。结果：过表达PHD1 可明显抑制NF-资B的活性
和I资B琢的降解，降低cyclin D1 的mRNA和蛋白表达水平；而干扰PHD1 的表达可显著增加NF-γB的活性，并上调cyclin D1 的
mRNA和蛋白表达水平，而不影响cyclinE1。过表达I资B琢SR 可以阻止干扰PHD1 引起的cyclinD1 mRNA水平的上调。过表达
PHD1 可引起细胞周期的停滞，显著抑制细胞的增殖和移植瘤的生长。结论：PHD1 可能通过下调NF-资B介导的cyclinD1的表达
抑制肺癌细胞的生长和增殖。 |
| 英文摘要: |
| Objective:To find new target for lung cancer treatment through investigating the function and the mechanism of
PHD1 in lung cancer cells. Methods:PHD1 was over expressed using the lipidosome or silenced using siRNA in A549 cells, then NF-资B
activity was detected by luciferase assay and the expression level of cyclinD1 was measured by real-time PCR and western blot. The
A549 stable cell line which expresses GFP-PHD1 was established and the cell cycle and cell growth were analyzed by flow cytometry.
Finally, the growth of tumor was observed after injecting cells subcutaneously to the nude mice. Results:Overexpression of PHD1
significantly inhibited the NF-资B activity and degradation of I资B琢, and decreased the mRNA and protein expression of cyclinD1;
Conversely, knocking down PHD1 significantly increased the NF-γB activity and up regulated the mRNA and protein expression of
cyclinD1, but it had no effect on the expression of cyclinE1. Over expression of IκBαSR inhibited the up regulation of cyclinD1 mRNA
level induced by knocking down of PHD1. Over expression of PHD1 caused cell cycle arrest and significantly inhibited the cell
proliferation and tumor growth. Conclusion:Over expression of PHD1 might inhibit the growth and proliferation of lung cancer cells
through down-regulating the cyclinD1 expression, which was mediated by NF-κB. |
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