Mifepristone inhibits proliferation, migration and invasion of HUUA cells and promotes its apoptosis by regulation of FAK and PI3K/AKT signaling pathway

Abstract

PurposeThe aim was to investigate mifepristone effects on endometrial carcinoma and the related mechanism.MethodsHHUA cells were treated with DMEM containing different concentrations of mifepristone. HHUA cells treated with 100 μmol/L mifepristone were named the Mifepristone group. HHUA cells co-transfected with pcDNA3.1-PI3K and pcDNA3.1-AKT overexpression vectors were treated with 100 μmol/L mifepristone and named the Mifepristone + PI3K/AKT group. mRNA expression was detected by quantitative reverse transcription PCR. Protein expression was performed by Western blot. Cell proliferation was conducted by MTT assay. Wound-healing assay was conducted. Transwell was used to detect cells migration and invasion. Apoptosis detection was performed by flow cytometry.ResultsMifepristone inhibited HHUA cells proliferation in a dose-dependent manner. Compared with HHUA cells treated with 0 μmol/L mifepristone, HHUA cells treated by 50–100 μmol/L mifepristone had a lower wound-healing rate, a greater number of migrating and invasive cells (P<0.01), as well as a higher percentage of apoptotic cells and Caspase-3 expression (P<0.01). When HHUA cells were treated with 50–100 μmol/L of mifepristone, FAK, p-FAK, p-PI3K and p-AKT relative expression was all significantly lower than HHUA cells treated with 0 μmol/L of mifepristone (P<0.01). Compared with the Mifepristone group, HHUA cells of the Mifepristone + PI3K/AKT group had a lower cell growth inhibition rate and percentage of apoptotic cells (P<0.01).ConclusionMifepristone inhibited HUUA cells proliferation, migration and invasion and promoted its apoptosis by regulation of FAK and PI3K/AKT signaling pathway.

Yueliang Yin Ameliorates Endometrial Receptivity in Mice with Embryo Implantation Failure by Reducing Pyroptosis and Activating BDNF/TrkB Pathway

“…In this study, the TUNEL assay showed that mifepristone induced apoptosis in endometrial cells, which is consistent with previous studies. [ 48 ] Immunofluorescence detection of caspase‐1 showed that mifepristone induced pyroptosis in endometrial cells. Further experiments revealed that GSDMD, cleaved caspase‐1, NLRP3, and IL‐1β expression levels were significantly elevated in mifepristone‐induced failure of implantation mice.…”

Advanced assessment of migration and invasion of cancer cells in response to mifepristone therapy using double fluorescence cytochemical labeling

“…MF was capable of diminishing cell migration through the 8 μm pore polycarbonate membrane as early as 6 h in each cell line studied. Supporting our data with ovarian, breast, glial, and prostate cancer cell lines, it was reported very recently that MF inhibited migration induced by progesterone in human astrocytoma cells [38], that both MF and its metabolite metapristone inhibited the chemotactic migration and mobility in SKOV-3 and IGROV-1 ovarian cancer cell lines facilitated by activation of the chemokine SDF-1/CXCR4 [29, 39], and that MF inhibited migration and invasion of endometrial carcinoma cells [40].…”

Involvement of the Estrogen and Progesterone Axis in Cancer Stemness: Elucidating Molecular Mechanisms and Clinical Significance

“…Moreover, mifepristone reduces the number of CSCs in cases of TNBC (174). Another study found that mifepristone inhibits the proliferation, migration, and invasion of endometrial cancer cells by blocking the PI3K/AKT pathways (175). Further, a recent genome-wide RNAi study demonstrated that mifepristone is one of the best drugs for inhibiting CSCs (176).…”