Objective Cytotoxin-associated protein (CagA) of H. pylori has been confirmed to be closely associated with gastric inflammation and tumorigenesis, but the mechanism behind it is little understood. In this study, we try to determine roles of CagA+ strain in activating PI3K/Akt1 signaling pathway, and affecting expression of p21WAF1/CIP1 and p27KIP1, and also in releasing IL-8 in host cells. Methods Akt1 phosphorylation and IL-8 levels of CagA+ and CagAˉ strain infected AGS cells were detected by ELISAs. Two quantitative RT-PCRs were established to measure p21WAF1/CIP1 and p27KIP1 mRNA levels in the CagA+ and CagAˉ strain infected cells. LY294002, an inhibitor of PI3K/Akt pathway, was used to define effect of the pathway in IL-8 release. Results CagA+ strain could induce an obvious elevation of Akt1 phosphorylation in the infected AGS cells while CagAˉ strain failed to do so. The CagA+ H. pylori strain infected AGS cells showed significant drops both in p21WAF1/CIP1 and p27KIP1 mRNA levels, whereas the CagAˉ H. pylori strain caused a remarkable increase in p21WAF1/CIP1 mRNA without affecting p27KIP1 gene transcription in the AGS cells. Both the CagA+ and CagAˉ H. pylori strains enabled AGS cells to produce close elevated levels of IL-8, and the LY294002 block resulted in unexpected elevations of IL-8 levels. Conclusion CagA can activate PI3K/Akt1 pathway that plays an inhibitory role in IL-8 release in H. pylori infected AGS cells. Activation of PI3K/Akt1 pathway and subsequent negative regulation of p21WAF1/CIP1 and p27KIP1 expression might be involved in CagA-associated carcinogenesis. Objective Cytotoxin-associated protein (CagA) of H. pylori has been confirmed to be closely associated with gastric inflammation and tumorigenesis, but the mechanism behind it is little understood. In this study, we try to determine roles of CagA + strain in activating PI3K / Akt1 signaling pathway, and affecting expression of p21WAF1 / CIP1 and p27KIP1, and also in releasing IL-8 in host cells. Methods Akt1 phosphorylation and IL-8 levels of CagA + and CagA strain infecting AGS cells were detected by ELISAs. Two quantitative RT- PCRs were established to measure the p21WAF1 / CIP1 and p27KIP1 mRNA levels in the CagA + and CagA ˉ strain infected cells. LY294002, an inhibitor of PI3K / Akt pathway, was used to define effect of the pathway in IL-8 release. an obvious elevation of Akt1 phosphorylation in the infected AGS cells while CagA ˉ strain failed to do so. The CagA + H. pylori strain infected AGS cells showed significant drops both in p21 WAF1 / CIP1 and p27KIP1 mRNA levels, whereas the CagA Â · H. pylori strain caused a remarkable increase in p21 WAF1 / CIP1 mRNA without affecting p27KIP1 gene transcription in the AGS cells. Both the CagA + and CagA ¯ H. pylori strains enabled AGS cells to produce close elevated levels of IL- and the LY294002 block resulted in unexpected elevations of IL-8 levels. Conclusion CagA can activate PI3K / Akt1 pathway that plays an inhibitory role in IL-8 release in H. pylori infected AGS cells. Activation of PI3K / Akt1 pathway and subsequent negative regulation of p21WAF1 / CIP1 and p27KIP1 expression might be involved in CagA-associated carcinogenesis.