This is the first evidence that Tan-Ⅰ induced apoptosis and promoted autophagy via the inactivation of PI3K/AKT/mTOR pathway on ovarian cancer and further inhibited tumour growth, which might be considered as effective strategy.
Curcumin can induce protective autophagy of human ovarian cancer cells by inhibiting the AKT/mTOR/p70S6K pathway, indicating the synergistic effects of curcumin and autophagy inhibition as a possible strategy to overcome the limits of current therapies in the eradication of epithelial ovarian cancer.
The addition of VEGF, IGF-1, and IL-8 weakened the inhibitory effect of DIRAS3 on ERK/AKT activity and reduced DIRAS3-mediated TFEB or FOXo3a nuclear localization and MAPLC3B expression in ovarian cancer cells.
Gentisyl Alcohol Inhibits Proliferation and Induces Apoptosis via Mitochondrial Dysfunction and Regulation of MAPK and PI3K/AKT Pathways in Epithelial Ovarian Cancer Cells.
The PI3K/AKT/mTOR signaling pathway is considered as a promising therapeutic target in the treatment of ovarian cancer (OC); however, inhibition of this pathway only exhibited moderate clinical efficacy when tested clinically.
Here, we outline the importance of PI3K/AKT/mTOR signaling pathway in OC tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in OC.
Taken all data together, these findings demonstrated that the absence of SMURF1 repressed cell proliferation, invasive capability, and EMT process in ovarian cancer through DAB2IP/AKT/Skp2 signaling loops, suggesting that SMURF1 may serve as a new potential therapeutic agent for ovarian cancer.
These data suggested that PI3K induced epithelial-to-mesenchymal transition and promoted cell migration and invasion by activating the PI3K/AKT pathway in ovarian cancer.
SNHG16 may activate phosphorylation of AKT and upregulate the expression of MMP9 to promote cell proliferation, invasion and migration of ovarian cancer.
KIAA0101 activated the PI3K/AKT/mTOR signaling pathway to inhibit cisplatin-induced apoptosis and autophagy in ovarian cancer cells resulting in cisplatin resistance.
We believe that GnRH agonists may be potential antitumor agents, and key factors in the PI3K/AKT-FOXO1 pathway may also be novel therapeutic targets for the treatment of EOC.
Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer.
During tumor progression, epithelial ovarian cancer (EOC) maintains E-cadherin expression and can positively affect EOC cell growth by contributing to PI3K/AKT activation.
Advanced EOCs were characterised by a heterogeneous kinase-driven metabolic signature and decreased phosphorylation of the AMPK-AKT-mTOR axis compared to early EOC (P<0.05 for AMPKα T172, AMPKα1 S485, AMPKβ1 S108, AKT S473 and T308, mTOR S2448, p70S6 S371, 4EBP1 S65, GSK-3 α/β S21/9, FOXO1 T24/FOXO3 T32, and FOXO1 S256).
Gene composition analyses of the disrupted modules revealed five common genes (mitogen‑activated protein kinase 1, phosphoinositide 3‑kinase‑encoding catalytic 110‑KDα, AKT serine/threonine kinase 1, cyclin D1 and tumor protein P53) across the four subtypes of ovarian cancer.
Therefore, we investigated the activation of mTOR complexes (mTORC1 and mTORC2) in a cohort of 156 EOC from Saudi Arabia by immunohistochemistry in a tissue microarray format. mTORC1 and mTORC2 were found to be activated in 55 of 146 (37.7%) and 63 of 140 (45%) of EOC samples, respectively. mTORC1 was significantly associated with mTORC2 (p < 0.0001) activation and both mTOR complexes were significantly associated with p-AKT (p = 0.0205 and 0.0298) and p-P70S6 (p < 0.0001 and 0.0035), respectively.