Department of Anesthesiology, First Affiliated Hospital, Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
J Exp Clin Cancer Res. 2012 Aug 19;31(1):66. doi: 10.1186/1756-9966-31-66.
Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, but the effect of propofol on gallbladder cancer is not clear. NF-E2-related factor 2 (Nrf2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. The aims of the current study were to evaluate effects of propofol on the behavior of human GC cells and role of Nrf2 in these effects.
The effects of propofol on cell proliferation, apoptosis, and invasion were detected by MTT assays, flow cytometry, and transwell assay. Also, activation of Nrf2 was determined by western blot, RT-PCR, and immunofluorescence assays. Nrf2 was knocked-down in GBC-SD cells by shRNA before evaluating the role of Nrf2 in the influence of propofol on biological behaviors.
Propofol promoted the proliferation of GBC-SD cells in a dose- and time- dependent manner. After exposure to propofol for 48 h, GBC-SD cells showed decreased apoptosis and increased invasion. Also, propofol over-expressed Nrf2 at both the protein and mRNA levels and induced translocation of Nrf2 into the nucleus. Finally, loss of Nrf2 by shRNA reversed the effect of propofol on cell proliferation, apoptosis, and invasion.
Propofol induces proliferation and promotes invasion of GC cells through activation of Nrf2.
异丙酚是癌症切除术手术中最常用的静脉麻醉剂之一,但异丙酚对胆囊癌的作用尚不清楚。核因子红细胞 2 相关因子 2(Nrf2)在癌细胞中大量表达,与增殖、侵袭和化疗耐药有关。本研究旨在评估异丙酚对人 GC 细胞行为的影响及 Nrf2 在这些作用中的作用。
通过 MTT 法、流式细胞术和 Transwell 法检测异丙酚对细胞增殖、凋亡和侵袭的影响。通过 Western blot、RT-PCR 和免疫荧光法测定 Nrf2 的激活。在评估 Nrf2 在异丙酚对细胞生物学行为影响中的作用之前,通过 shRNA 敲低 GBC-SD 细胞中的 Nrf2。
异丙酚呈剂量和时间依赖性地促进 GBC-SD 细胞的增殖。暴露于异丙酚 48 h 后,GBC-SD 细胞凋亡减少,侵袭增加。此外,异丙酚在蛋白和 mRNA 水平上均过度表达 Nrf2,并诱导 Nrf2 向核内易位。最后,shRNA 敲低 Nrf2 逆转了异丙酚对细胞增殖、凋亡和侵袭的影响。
异丙酚通过激活 Nrf2 诱导 GC 细胞增殖并促进其侵袭。