Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells

Abstract

Gastric cancer, one of the most common malignancies worldwide, typically has a poor prognosis and poor survival rate. Previous studies have investigated the chemopreventive effect of celecoxib. In the present study, the SGC-7901 human gastric cancer cell line was utilized to examine the chemopreventive mechanisms of celecoxib. The inhibition of cell proliferation was determined using MTT assay, cell apoptosis was monitored by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and flow cytometry, and cell ultrastructural changes were assessed via transmission electron microscopy. The mRNA expression of Akt, caspase-8 and -9 was examined using quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) and p-Akt, procaspase-8 and -9 were analyzed via western blotting. The results showed that celecoxib inhibited the proliferation of SGC-7901 cells in a time- and dose-dependent manner. Additionally, celecoxib induced apoptosis as substantiated by typical apoptotic bodies, autophagosomes and an increased apoptotic rate. It was found that following celecoxib treatment, Akt mRNA expression was not significantly altered, and that p-Akt protein levels decreased in a time- and dose-dependent manner. Additionally, caspase-8 and -9 mRNA expression was significantly increased, while procaspase-8 and -9 protein expression decreased relative to the time- and dose-dependent effects. These results demonstrated that celecoxib induced apoptosis and autophagy of gastric cancer cells in vitro through the PI3K/Akt signaling pathway. Moreover, our findings suggested that celecoxib induces apoptosis in gastric cancer cells through the mitochondrial and death receptor pathways, providing additional understanding regarding the chemopreventive behaviors of celecoxib and its uses in cancer therapy.

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

“…Focusing on dysregulation mRNAs through GO and Pathway analysis, the GO results suggested the functions of significant differences in the aspects of immune functions, metabolism and cellular functions, the significant differences in the pathways mainly focus on cancer-related pathways such as 'PI3K-Akt signaling pathway, Wnt signaling pathway, pathways in cancer and small cell lung cancer'. Many pathway-related analysis of the GC significant difference genes, Liu et al (41) and Ren et al (42), also found 'PI3K-Akt signaling pathway and Wnt signaling pathway' were related with GC cell functions.…”

Anti-cancer effect of low dose of celecoxib may be associated with lnc-SCD-1:13 and lnc-PTMS-1:3 but not COX-2 in NCI-N87 cells

“…Similarly, Cho et al (20) demonstrated the anti-cancer effect of celecoxib on GC cells (AGS and MKN-45) by regulating cell-cycle arrest and apoptosis. In addition, Liu et al (11) suggested that celecoxib induced apoptosis through the mitochondrial and death receptor pathways in GC cells. These results indicated that a low dose of celecoxib may have a chemopreventive function in the development of GC by regulating cell cycle and apoptosis.…”

“…In addition to aspirin, celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to be involved in uncontrolled cell proliferation, apoptosis, angiogenesis and metastasis (9,10). Previous studies have suggested that celecoxib is able to induce cell apoptosis through the phosphoinositide 3 kinase/Akt signaling pathway (11) and to inhibit invasion through the adenine nucleotide translocator-dependent signaling pathway in GC cells (12). In addition, celecoxib has been reported to be able to prevent the development of GC in rats (13).…”

“…The cells (5x10 3 ) were seeded into each well of a 96-well plate and cultured in DMEM supplemented with 10% FBS. Following 24 h of culture at 37˚C and 5% CO 2 with saturated humidity, the cells were treated with 0 (control group), 15, 30 and 60 µM celecoxib (Sigma-Aldrich; Merck KGaA, Darmstadt, Germany), and subsequently incubated for 72 h (37˚C, 5% CO 2 with saturated humidity) (11). MTT (10 µl, 5 mg/ml; Shanghai Sangon Biotech Co., Ltd, Shanghai, China) was added to each well at the same time, and the cells were subsequently incubated for 4 h at 37˚C.…”

Human bocavirus induces apoptosis and autophagy in human bronchial epithelial cells

“…Previous studies have demonstrated that celecoxib and caffeine induced autophagy through inhibition of the PI3K/ATK signaling pathway (17,18). The PI3K/AKT signaling pathway is widely utilized in normal and abnormally activated cells, such as in cancer cells (19).…”