Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-κB signal

Abstract

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.

Propofol inhibits pancreatic cancer proliferation and metastasis by up‐regulating miR‐328 and down‐regulating ADAM8

“…In fact, several previous studies have implicated the functions of propofol on miRNA expression. For example, miR‐372, miR‐195, miR‐1284, miR‐206, miR‐9 and miR‐21 were all stated to be affected by propofol to control cell growth, migration and invasion . Additionally, here ADAM8 was identified to directly target to miR‐328.…”

“…For example, miR-372, miR-195, miR-1284, miR-206, miR-9 and miR-21 were all stated to be affected by propofol to control cell growth, migration and invasion. [14][15][16][17][18][19] Additionally, here ADAM8 was identified to directly target to miR-328. Our results implicate that propofol exerts an inhibitory effect on pancreatic cancer cell growth, migration and invasion by enhancing miR-328 which targets ADAM8.…”

The mechanism of propofol in cancer development: An updated review

“…Propofol was also found to inactivate the NF‐κB pathway and then lead to pancreatic cancer cell apoptosis and gemcitabine chemosensitization . As mentioned above, in ovarian cancer cells, propofol has been reported to inhibit NF‐κB activation by upregulating miR‐9 expression …”

“…It is well known that epigenetic alterations or genetic modulation of epigenetic regulators plays important roles in carcinogenesis . Many studies show that the anticancer effect of propofol is potentially due to regulation of the epigenetic pathway in cancer …”

“…Huang et al. proved that propofol could upregulate miR‐9 expression and then lead to cell apoptosis and inhibition of cell growth and invasion in ovarian cancer cells …”