Propofol inhibits proliferation, migration, invasion and promotes apoptosis by regulating HOST2/JAK2/STAT3 signaling pathway in ovarian cancer cells.

Abstract

We aimed to investigate the effect of propofol on the growth of human ovarian cancer cells ES2 and OVCAR-3 in vitro by regulating long non-coding RNA HOST2 (human ovarian cancer-specific transcript 2) and the inhibition of JAK2/STAT3 signaling pathway. In the present study, ES-2 and OVCAR-3 cells were firstly treated with different concentrations of propofol (0, 1, 5 and 10μg/ml). The expression of HOST2 in ES-2 and OVCAR-3 cells were detected by quantitative reverse transcription-PCR (qRT-PCR). Then, the expression of HOST2 was changed by transfection of HOST2 overexpression plasmid into ES-2 and OVCAR-3 cells. Cell proliferation, migration, invasion and apoptosis were performed using CCK-8, wound-healing, Transwell assays and Flow Cytometry. Western blot analysis was performed to detect the expressions of apoptosis-associated proteins and JAK2/STAT3 pathway-related proteins. Results showed that cell viability and intracellular HOST2 expression in ES-2 and OVCAR-3 cells were decreased gradually with the increase of propofol concentration in a dose-dependent manner. Compared with the propofol group, overexpression of HOST2 significantly promoted the cell proliferation, migration, invasion and inhibited apoptosis, and ameliorated the inhibitory effect of propofol on the growth of tumor cells. Western blot analysis showed that compared with propofol group, the expression of Bcl-2 was significantly increased whereas Bax and the ratio of Cleaved caspase3/caspase3 were significantly decreased in pcDNA-HOST2 group. In addition, overexpression of HOST2 significantly enhanced the phosphorylation level of JAK2 and STAT3, and reduced the suppressive effect of propofol on JAK2/STAT3 signaling. Our results illustrated that propofol could significantly inhibit the proliferation, migration, invasion and induce apoptosis of ES-2 and OVCAR-3 cells by downregulating HOST2. The regulation mechanism may be achieved by inhibiting the activation of JAK2/STAT3 signaling pathway.