Zimin Liu1, Jian Zhang2, Guangchen Hong3, Jinping Quan2, Lin Zhang1, Meiqin Yu4. 1. Department of Oncology, The Affiliated Hospital of Qingdao University Qingdao, Shandong, China. 2. Department of General Surgery, The Affiliated Hospital of Qingdao University Qingdao, Shandong, China. 3. Department of General Surgery, People's Hospital of Shinan District Qingdao, Shandong, China. 4. Department of Clinical Laboratory, Women and Children's Hospital of Qingdao Qingdao, Shandong, China.
Abstract
AIM: Propofol, an intravenous anesthetic agent, has been found to inhibit invasion and growth of pancreatic cancer cells in 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.
AIM: Propofol, an intravenous anesthetic agent, has been found to inhibit invasion and growth of pancreatic cancer cells in 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.
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