Propofol inhibits growth and invasion of pancreatic cancer cells through regulation of the miR-21/Slug signaling pathway.
OBJECTIVE
Propofol, an intravenous anesthetic agent, has been found to inhibit invasion and growth of pancreatic cancer cellsin vitro. However, the mechanisms underlying these tumor-promoting phenotypes are not known. The microRNA miR-21 has been reported to be overexpressed in pancreatic cancer, and overexpression of miR-21 confers a poor prognosis to patients with pancreatic cancer. Further studies have identified the E-cadherin transcription repressor Slug as a direct target of miR-21. In this study, we assessed whether propofol inhibits invasion and growth of pancreatic cancer cells by regulation of miR-21/Slug signaling.


METHODS
PANC-1 pancreatic cancer cells were treated with different concentrations of propofol (1, 5 or 10 μg/mL) for 48 h, or 10 μg/mL propofol for 12, 24 or 36 h. Cell survival and apoptosis were detected by LDH release, BrdU cell proliferation and flow cytometry assays; cell invasion and migration were detected by transwell migration assays. miR-21 mimic (miR-21), Slug cDNA, PUMA siRNA and E-cadherin siRNA transfection was used to assess the signaling pathway in which propofol functions in PANC-1 cells. Protein and mRNA expression, respectively, were detected by western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays.


RESULTS
Propofol inhibited growth and invasion, and induced apoptosis, in a dose- and time-dependent manner in PANC-1 cells. Propofol inhibited miR-21 levels and decreased Slug expression, resulting in an increase in Slug-dependent PUMA and E-cadherin expression in PANC-1 cells. miR-21 overexpression or PUMA or E-cadherin silencing impaired propofol-induced cell apoptosis, growth and invasion. Re-expression of Slug attenuated the expression of PUMA and E-cadherin that was induced by propofol treatment, the reduction of growth and invasion, and the increase in cell apoptosis.


CONCLUSIONS
Propofol can effectively inhibit invasion and induce apoptosis of PANC-1 cells by regulating miR-21/Slug signals.
Department of Oncology, The Affiliated Hospital of Qingdao University Qingdao, Shandong, China.
Zimin
Z
Liu
Department of General Surgery, The Affiliated Hospital of Qingdao University Qingdao, Shandong, China.
Jian
J
Zhang
Department of General Surgery, People's Hospital of Shinan District Qingdao, Shandong, China.
Guangchen
G
Hong
Department of General Surgery, The Affiliated Hospital of Qingdao University Qingdao, Shandong, China.
Jinping
J
Quan
Department of Oncology, The Affiliated Hospital of Qingdao University Qingdao, Shandong, China.
Lin
L
Zhang
Department of Clinical Laboratory, Women and Children's Hospital of Qingdao Qingdao, Shandong, China.
Meiqin
M
Yu
E-cadherin; PUMA; Propofol; apoptosis; invasion; miR-21; pancreatic cancer; slug