Bcl-2 associated athanogene 4 regulates self-renewal in gastric cancer stem cells

Abstract:

Objective To investigate the role of Bcl-2 associated athanogene 4（BAG4） in self-renewal capacity of gastric cancer stem cells（GCSCs）.Methods GCSCs were isolated/enriched using sphere forming culture system， and their biological characteristics were identified. BAG4-knockdown MGC803 gastric cancer cell lines were constructed by lentivirus interference technique. Colony and tumor sphere formation assay were used to estimate the effect of BAG4-knockdown on self-renewal capacity of gastric cancer in vitro.Results We successfully isolated/enriched sphere cells（SC） using sphere forming culture system. MGC803-SC showed higher expression level of stem-related genes Sox2， Oct4 and Bmi1 than normal adherent cells， and showed stronger clone-formation ability（198±17 vs. 92±11，P<0.001）. After induction of differentiation， the expression of CD44 decreased，and showed stronger invasion ability in vitro（185±18 vs. 84±11，P<0.01）. The above experimental results confirmed that MGC803-SC had GCSCs properties. The expression level of BAG4 in GCSCs was significantly higher than that in normal adherent gastric cancer cells.Conclusion Silencing BAG4 gene can effectively inhibit the self-renewal ability of GCSCs，suggesting that BAG4 might be a promising target for gastric cancer therapy.