Published online Sep 15, 2023. doi: 10.4251/wjgo.v15.i9.1544
Peer-review started: April 11, 2023
First decision: July 9, 2023
Revised: July 14, 2023
Accepted: July 28, 2023
Article in press: July 28, 2023
Published online: September 15, 2023
Processing time: 154 Days and 19.9 Hours
Gastric cancer (GC) is one of the most common malignant tumors. Osteopontin (OPN) is thought to be closely related to the occurrence, metastasis and prognosis of many types of tumors.
To investigate the effects of OPN on the proliferation, invasion and migration of GC cells and its possible mechanism.
The mRNA and protein expression of OPN in the GC cells were analyzed by real-time quantitative-reverse transcription polymerase chain reaction and western blotting, and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC. Next, the effects of OPN knockdown on GC cells migration and invasion were examined. The short hairpin RNA (shRNA) and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer’s instructions. Non transfected cells were classified as control in the identical transfecting process. 24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay, and cell invasiveness and migration were detected by Trans well assay. Meanwhile, the expression of protein kinase B (AKT), matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting.
The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells. OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation, invasion and migration of SGC-7901 cells. Moreover, in the experiments of investigating the underlying mechanism, results showed that OPN knockdown could down-regulated the expression of MMP-2 and VEGF, it also decreased the phosphorylation of AKT. Meanwhile, the protein expression levels of MMP-2, VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002).
These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to up-regulate MMP-2 and VEGF expression, which contribute SGC-7901 cells to proliferation, invasion and migration. Thus, our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.
Core Tip: We investigated the effects of osteopontin (OPN) on the proliferation, invasion and migration of gastric cancer (GC) cells and its possible mechanism. The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells. OPN knockdown by specific short hairpin RNA noticeably reduced the capabilities of proliferation, invasion and migration of SGC-7901 cells. Moreover, our results showed that OPN though phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway signal pathway to up-regulate matrix metalloproteinase 2 and vascular endothelial growth factor expression, which contribute SGC-7901 cells to proliferation, invasion and migration. These results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.