To define the inhibitory and pro-apoptotic effects of the two PI3K inhibitors BEZ235 and BKM120 in three human colon cancer (HT-29, HCT-116 and DLD-1) and three gastric cancer (NCI-n87, AGS and MKN-45), cell lines with different PIK3CA gene mutation status were used.
Thus far, the human epidermal growth factor receptor (HER) pathway, angiogenic pathway, and phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin pathway have emerged as potential avenues for targeted therapy in AGC patients.
Through in vitro experiments, we proved that m6A suppression (represented by METTL14 knockdown) promoted GC cell proliferation and invasiveness through activating Wnt and PI3K-Akt signaling, while m6A elevation (represented by FTO knockdown) reversed these phenotypical and molecular changes. m6A may also be involved in interferon signaling and immune responses of GC.
This study revealed that (1) PIK3CA hotspot mutations occurred with low frequency in gastric cancer; (2) PIK3CA hotspot mutations were not directly associated with PI3K pathway activation; and (3) p-AKT (+) may be a biomarker for better outcomes for gastric cancer patients undergoing gastrectomy regardless of the PIK3CA mutation status.
This study demonstrates, for the first time, that SHIP2 is frequently downregulated in gastric cancer, and reduced SHIP2 expression promotes tumorigenesis and proliferation of gastric cancer via activation of the PI3K/Akt signaling.
This is the first time this extensive panel of 9 genes within PI3K/AKT/mTOR pathway has been studied in GC to clarify the biological role of this pathway in GC and develop new strategies for this malignancy.
These results show that H. pylori infection induces AKT/PI3K-mediated phosphorylation of p27 at T157 and T198 to cause cytoplasmic p27 mislocalization in gastric cancer, and that p27 mislocalization is an adverse prognostic feature in gastric cancer.
Therefore, how PTEN lipid phosphatase inactivation contributes to the occurrence and development of gastric cancer and the potential role of the Hippo and PI3K/Akt pathways in PTEN lipid phosphatase inactivation mediated gastric tumorigenesis remain to be explored.
The mechanism analyses further found that SLC25A5-AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR-19a-3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC.
The HER-2 positive SGC-7901 secreted more transforming growth factor beta 1 (TGF-β1) and resultantly activated MMP-9 to enhance s-ICAM-1 secretion and further studies showed that phosphatidylinositol-3 kinase (PI3K)/Akt/NF-κB signaling pathway was involved in GC pathogenesis.
The expression of phosphatidylinositol 3' -kinase (PI3K)/ protein kinase B (AKT) and c-Jun N-terminal kinase (JNK) was down-regulated by GEN (all P < .05) while reversed by HULC overexpression.HULC was up-regulated in GC.
The experimental methods are as follows: (1) The proliferation of HGC-27 cells inhibited by Apatinib and LY294002 was observed by 3-(4,5)-dimethylthiahiazo-(z-y1)-3,5-diphenytetrazoli- umromide (MTT) assay; (2) flow cytometry was adopted to detect the apoptosis of cells after they were treated with drugs and the positive control; (3) different effects of varying concentrations of Apatinib on apoptosis-related genes and proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine-aspartic acid protease (Caspase) 9, were detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting (WB), and the effects of different concentrations of Apatinib on the protein expressions of PI3K, phosphorylated (p)-PI3K, Akt and p-Akt were detected by Western blotting.
The effects of miR-34a ectopic expression on the AKT and p-AKT expression of cisplatin-induce gastric cancer cells were determined by Western blot and flow cytometry with the PI3K pathway inhibitor Wortmannin.
The cooperation between RUNX3 and the PI3K/Akt signaling pathway component FoxO3a/FKHRL1 suggests the putative role of RUNX3 in the homoeostasis of gastric cells and in stomach cancer control.
The aim of the present study was to investigate the mechanism of microRNA-4295 (miR-4295), which regulates cisplatin (DDP)-induced apoptosis in GC cells through the leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1)-mediated epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.