Interleukin-8 Regulates the Autophagy and Apoptosis in Gastric Cancer Cells via Regulating PI3K/Akt Signaling Pathway.

Abstract

Objective To explore the role and mechanism of interleukin-8-mediated autophagy regulation of gastric cancer (GC) cells in GC. Methods After cell culture, the SGC7901 cell line was separated into the control group and IL-8 (20 ng/mL) group, IL-8 (40 ng/mL) group, and IL-8 (60 ng/mL) group, to verify the effects of the PI3K/Akt signal path on the modulation of autophagy in GC cells. Western blot detected autophagy markers, ATG12-ATG5 complexes, autophagy-associated pathways, and apoptosis-associated factors in GC cells. Transwell was utilized to identify invasion capability. Results Compared with the control group, the expression of LC3II, Atg5, ATG7, Beclin1, Bax, C-cas3, C-cas9, P-PI3K, P-Akt, and ATG12-ATG5 was remarkably elevated in the IL-8 (60 ng/mL) group, IL-8 (20 ng/mL) group, and the IL-8 (40 ng/mL) group. The expression of P62 and Bcl-2 in the IL-8 (60 ng/mL) group was also lower than that of the IL-8 (20 ng/mL) group and IL-8 (40 ng/mL) group, in contrast to the controls. The invasive quantity of GC SGC7901 cells in the IL-8 (60 ng/mL) group was also remarkably higher in contrast to the IL-8 (20 ng/mL) and IL-8 (40 ng/mL) groups. The relative expressions of LC3II, Atg5, ATG7, Beclin1, Bax, C-cas3, C-cas9, P-PI3K, P-Akt, and ATG12-ATG5 complex proteins in LY294002 group were considerably elevated. LC3II, Atg5, ATG7, Beclin1, Bax, C-cas3, C-cas9, P-PI3K, P-Akt, and ATG12-ATG5 were decreased in the IL-8 + LY294002 group. The relative expressions of P62 and Bcl-2 proteins in the IL-8 + LY294002 group were remarkably elevated, and the invasion of SGC7901 cells in the IL-8 group was elevated. In contrast to the IL-8 group, the invasion quantity of gastric cancer SGC7901 cells in the IL-8 + LY294002 group was considerably decreased. Conclusion IL-8 promotes autophagy and aggression and suppresses apoptosis of GC SGC7901 cells by regulating PI3K/AKT pathway phosphorylation.