PlGF knockdown induced apoptosis through Wnt signaling pathway in gastric cancer stem cells

Abstract

Despite the fact that much research has focused on gastric cancer, it is still a worldwide concern, because of the difficulties with factors such as signaling pathway crosstalk and gastric cancer stem cell (GCSC). Placental growth factor (PlGF) is one of these factors, and its tumorigenicity potential still remains a question. As a result, we have investigated the effect of PlGF knockdown on apoptosis and genes involved in the Wnt signaling pathway, and apoptosis in cancer stem cells derived from AGS an MKN-45 gastric cancer cell lines. We isolated GCSCs from MKN-45 and AGS cell lines on a nonadherent surface. Then the cell viability, the real-time reverse transcription-polymerase chain reaction data of the genes involved in the Wnt signaling pathway, and apoptosis were evaluated. Furthermore, DNA laddering was used to show the apoptotic effect and DNA fragmentation caused by the PlGF knockdown. Our investigation revealed that the PlGF knockdown with PlGF-specific small interfering RNA at 40 pmol for GCSCs derived from MKN-45 and AGS at 24 hours can significantly affect the cell viability, the Wnt signaling pathway, and the apoptosis-related genes expression. In conclusion, we showed the PlGF knockdown may induce apoptosis via the Wnt signaling pathway in GCSCs.

Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression

“…Nonetheless, the direct role of PlGF in cancer remains unclear. In fact, PlGF overexpression has been shown to result in tumor growth promotion or inhibition, perhaps due to context-dependent effects of this growth factor in tumor progression [169,223,224,225,226,227,228]. In addition, studies in transgenic mice revealed that the angiogenic activity of PlGF is restricted to pathological conditions since PlGF expression is low to undetectable in most tissue in normal health [84,85].…”

Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity

“…(18) PlGF also acts as a J o u r n a l P r e -p r o o f survival factor in tumor cells (19) and in a variety of cell types. (13,20) In the current study, whereas PlGF-knockdown caused no alteration in the proliferation rate of hTERT-RPE1 cells, it enhanced serum starvation-induced apoptosis in RPE cells, which was reversed by replenishment of PlGF-1 and PlGF-2. In addition, PlGFknockdown enhanced the activation of caspases 3 and/or 7, both of which are executioner caspases carrying out the apoptosis cascade.…”

“…In addition, PlGF deficiency has been reported to lead to increased apoptosis and necrosis in vascular endothelial cells and macrophages ( 18 ). PlGF also acts as a survival factor in tumor cells ( 19 ) and in a variety of cell types ( 13 , 20 ). In the current study, whereas PlGF-knockdown caused no alteration in the proliferation rate of hTERT-RPE1 cells, it enhanced serum starvation–induced apoptosis in RPE cells, which was reversed by replenishment of PlGF-1 and PlGF-2.…”

lncRNA HOXC‐AS1 promotes gastric cancer via binding eIF4AIII by activating Wnt/β‐catenin signaling

“…The Wnt/β‐catenin signaling pathway was previously reported to participate in cellular functions crucial for normal organ development, such as cell survival, apoptosis, proliferation, metastasis, the EMT process and differentiation 13,14 . To be more specific, Wnt/β‐catenin signaling activation has been reported to enhance cell viability, the EMT process and inhibit cell apoptosis in GC 15 .…”