Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Abstract

ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (ddP) resistance in ovarian cancer cells. ovarian cancer cell viability was assessed by the cell counting kit-8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)-374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription-quantitative Pcr; the binding ability of miR-374a to FOXO1 was assessed by the dual-luciferase reporter assay; cellular sensitivity to ddP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl-2-like-protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased mir-374a expression levels in A2780 cells. In addition, the viability of a2780/ddP cells in the propofol + ddP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR-374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. conversely, genetic knockdown of miR-374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, mir-374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. in addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. in conclusion, propofol downregulated mir-374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

Propofol‑induced miR‑125a‑5p inhibits the proliferation and metastasis of ovarian cancer by suppressing LIN28B

“…Propofol not only has an anesthetic effect but has also been reported to possess antioxidant, neuroprotective, immunomodulatory, analgesic, antiemetic and anticancer effects (6,28,29). Previous studies have also reported that propofol can suppress tumor growth (25,30,31). another study revealed that propofol increased the expression of caspase-3 in A549 cells and loVo cells to induce cell apoptosis (32).…”

“…Huang et al (37) revealed that propofol upregulated miR-9 expression and led to the inhibition of cell proliferation and invasion in ovarian cancer eS-2 cells. Moreover, Sun et al (31) found that propofol could decrease miR-374a expression to increase the expression of forkhead box O1, resulting in inhibition of cisplatin resistance and proliferation. The present study evaluated the effects of different concentrations of propofol on two ovarian cell lines.…”

“…mirnas, which are non-coding rnas consisting of 18-25 nucleotides, act as oncogenes or tumor suppressors and can be used as potential biological markers to diagnose, predict and treat different cancer types (38). Previous studies have reported that several mirnas are regulated by propofol (25,31). The present study analyzed mrna sequencing data from 453 patients with ovarian cancer in TcGa.…”

“…Propofol also upregulates the expression of miR-125a-5p to inhibit LIN28B. Therefore, propofol in the surgical treatment of ovarian cancer may be a potential target for improving cancer prognosis and survival (24,31,41).…”

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

“…Propofol played an anti-tumor role in a variety of cancers through suppressing the growth of tumors [2,34], inducing the apoptosis of cancer cells [2,20] and inhibiting the metastasis of cancer cells [27,28]. The anti-tumor role of Propofol in ovarian cancer has also been reported before [11,24,27]. For instance, Huang et al claimed that Propofol hampered the invasion and proliferation of ovarian cancer cells through modulating miR-9/NF-κB signaling [11].…”