Impact of isoflurane on malignant capability of ovarian cancer in vitro

Background. Metastatic recurrence of ovarian cancer is the foremost cause of postoperative mortality. With recent research indicating that inhalation of anaesthetics may influence cancer cell behaviour, this study investigated the effects of isoflurane on the expression of tumorigenic markers and proliferative capacity in ovarian cancer cells. Methods. Ovarian cancer (SK-OV3) cells were cultured and then exposed to 2% isoflurane for 2 h. The expression of markers involved in cell proliferation, angiogenesis, and migration were assessed up to 24 h after treatment using immunofluorescence staining, western blotting, and flow cytometry. The effects of isoflurane on in vitro angiogenesis and migration were also determined. Results. Isoflurane exposure significantly increased insulin-like growth factor (IGF)-1 and IGF-1R expression, cell cycle progression, and cell proliferation in SK-OV3 cells. Increased expression of the angiogenic markers vascular endothelial growth factor (VEGF) by 56% (P<0.05) and angiopoietin-1 by 62% (P<0.05) was also observed 24 h after isoflurane exposure together with an enhanced in vitro angiogenesis. Cell migration was significantly increased after exposure to isoflurane together with increased production of both matrix metalloproteinases 2 and 9 (both P<0.05) by almost five-fold relative to control. These effects were abolished when IGF-1R signalling was blocked either by neutralizing antibody or by small interfering RNA. Conclusions. Our data indicate that isoflurane increases the malignant potential of ovarian cancer cells through the up-regulation of markers associated with the cell cycle, proliferation, and angiogenesis. This study warrants further investigations.