Upregulated Expression Of Periostin By Hypoxia In Non-small-cell Lung Cancer Cells Promotes Cell Survival Via The Akt/PKB Pathway

Tumorigenesis in human is a multistep process that involves the sequential acquisition of a number of genetic,epigenetic or somatic alterations as a result of increasing genomic instability.Tumor cells can form a microenvironment of the tumor-host interface by the interaction with the various components of extracellular matrix,and coordinate the adaptive growth of cells response to different microenvironment through the regulating a variety of intracellular pathways.Based on the unique physiological characteristic of tumor microenvironment,it shows a great influence in tumorigenisis.Hypoxia as one of the salient features of tumor microenvironment plays a critical role in cell proliferation,survival,angiogenesis, immune surveillance,metabolism,as well as tumor invasion and metastasis.As a member of matricellular proteins in extracellular matrix,periostin has been shown to be frequently overexpressed in various types of human cancers.We have previously reported that periostin potently promotes metastatic growth of colon cancer by augmenting cell survival.However,little is known about the functions of periostin in lung cancer.Here,we used CoCl₂ and DFO to induce a chemical-mimic hypoxia in nonsmall-cell lung cancer A549 cells,and apply the techniques of western blot,RNA interference,Apoalert DNA Fragmentation Assay Kit and Hoechst staining studied the function and molecular mechanism of periostin on survival of A549 cells under hypoxia stress.The result showed that increased expression of periostin in A549 cells was one kind of cellular responses to the stress of chemical-mimic hypoxia,and this effect could be regulated by hypoxia inducible growth factors,such as TGF-αand bFGF.We further demonstrated that RTK/PI3-K pathway activated by TGF-αand bFGF was evoked in upregulating the expression of periostin,and then periostin promoted the survival of A549 cells under hypoxia microenvironment via activation of Akt/PKB pathway.Therefore,periostin and the pathway that it involved might provide a target for lung cancer treatment.