Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Yue-Chao Qin; Xin Yan; Xiao-Lin Yuan; Wei-Wei Yu; Fan-Jie Qu

doi:10.4251/wjgo.v15.i9.1544

Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

World J Gastrointest Oncol. 2023 Sep 15;15(9):1544-1555. doi: 10.4251/wjgo.v15.i9.1544.

Authors

Yue-Chao Qin^{1

2}, Xin Yan¹, Xiao-Lin Yuan², Wei-Wei Yu¹, Fan-Jie Qu³

Affiliations

¹ Department of Oncology, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
² Research Center, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, China.
³ Department of Oncology, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China. wyb960419@163.com.

Abstract

Background: 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.

Aim: To investigate the effects of OPN on the proliferation, invasion and migration of GC cells and its possible mechanism.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Gastric cancer; Invasion; Migration; Osteopontin; Phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway; Proliferation.