Epstein-Barr virus BZLF1 promotes the growth of gastric cancer cells through activa-tion of the PI3K/AKT signaling pathway / 中国肿瘤临床

ABSTRACT

Objective: To explore the effect of the Epstein-Barr virus (EBV) BZLF1 gene on the biological behavior of EBV-negative gas-tric cancer cells and the underlying molecular mechanism. Methods: Lentiviral overexpressing BZLF1 was used to infect AGS and HGC27 gastric cancer cell lines. And the cell proliferation, apoptosis and migration invasive ability, and expression changes of cell sig-naling pathway were detected by CCK8 assay, apoptosis detection, migration and invasion assay, as well as western blot. HGC27 cells overexpressing BZLF1 were injected into the dorsal of NOD/SCID mice to construct xenografts, and the effect of BZLF1 on tumor growth was observed. Results: The expression of BZLF1 protein was significantly up-regulated in AGS-BZLF1 and HGC27-BZLF1 infected by over-expressing BZLF1 lentivirus. The cell proliferation in vitro and the tumorigenic ability in mice were significantly increased (P<0.05). Apoptosis was inhibited by BZLF1 protein, and the apoptotic rate of AGS-BZLF1 and HGC27-BZLF1 was (2.40±0.14)% and (3.90± 0.14)%, which was significantly lower than (5.75±0.35)% and (9.70 ± 0.42)% of AGS and HGC cells (P<0.05); however, there was no sig-nificant change in cell migration and invasion ability. In-depth molecular mechanism studies found that PI3K/AKT signaling pathway was significantly activated with enhanced pAKT and pS6 expression. After blocking the PI3K/AKT signaling pathway with BEZ235 inhibi-tor, the growth of HGC27-BZLF1 and AGS-BZLF1 cells was inhibited. Conclusions: EBV BZLF1 may promote the growth of gastric cancer cells by activating the PI3K/AKT signaling pathway and targeting PI3K/AKT pathway inhibitors, and serve as a promising treatment op-tion for EBV-associated gastric carcinoma.