Effect of propofol on phosphatidyl inositol 3-serine kinase/protein kinase signaling pathway in breast tumor cells

Abstract

Objective To study the effect of propofol on phosphatidyl inositol 3-serine kinase/protein kinase (PI3K/AKT) signaling pathway mediated by γ-aminobutyric acid receptors on breast cancer cell michigan cancer foundation-7 (MCF-7 cell) surface and to understand whether it presents inhibitory effect on proliferation of breast cancer cells. Methods According to the concentration of propofol, it is classified into propofol groups of 100 μmol/L, 300 μmol/L, 1 mmol/L, as well as 3 mmol/L. Set up blank control group without the intervention of propofol and intervention groups with different concentrations of propofol + γ-aminobutyric acid antagonist bicuculline. Apply whole-cell patch clamp technique to observe the effect of different concentrations of propofol in the intervention groups, control group as well as propofol combined with γ-aminobutyric acid antagonist group on chloride channels on the surface of MCF-7 cell membrane. Use protein signet ring method to detect the expression of Akt protein in the PI3K/Akt signaling path within MCF-7 cells. Use methyl thiazol tetrazolium (MTT) method to determine the effect of propofol on MCF-7 cell viability; compared both of them. Results (1) With the increase of cell membrane potential, propofol shall concentration-dependently simulate the chlorine ion current intensity in MCF-7 cells, with chlorine ion current intensity in MCF-7 cells of 3 mmol/L propofol group showing the intensity was (40.13±9.21) Pa, the control group showing the intensity was (19.46±8.53) Pa, the maximum difference compared to the control group, and the difference was statistically significant (P=0.032); after adding γ-aminobutyric acid antagonist bicuculline, the effect of propofol on the chlorine ion current intensity in MCF-7 cells weakened, but it had no significant difference with the 3mmol/L propofol group (16.92±7.47) Pa and the control group (18.61±8.19) Pa, (P=0.063); (2) Protein signet ring method showed that propofol has inhibitory effect in Akt protein expression in PI3K/Akt signaling pathway of MCF-7 cells; (3) The inhibitory effect of propofol on the survival of MCF-7 cells shall increase with the concentration of propofol. (4) The immunohistochemistry results showed that, breast cancer MCF-7 cells in propofol group was significantly lower than that of the control group when exposing tumor tissue to propofol for 72 h. Conclusion By stimulating the opening of chloride channel in MCF-7 cells, propofol of high concentration shall intensify its interation with γ-aminobutyric acid receptors in breast cancer cell surface to inhibit the activity of PI3K/Akt signaling pathway, and ultimately inhibit breast cancer cell proliferation. Key words: Propofol; Breast cancer cells; Phosphatidyl inositol 3-serine kinase/protein kinase signaling pathway; Cell proliferation