Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Propofol induces proliferation and promotes invasion of GC cells through activation of Nrf2.
Department of Anesthesiology, First Affiliated Hospital, Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
Lingmin
L
Zhang
Ning
N
Wang
Suna
S
Zhou
Wenguang
W
Ye
Guixia
G
Jing
Mingxin
M
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D015742:Propofol / Q000008:administration & dosage*
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D015742:Propofol