Akt2 overexpression correlates with chemoresistance of colorectal cancer (CRC). However, the cellular functions and precise signals elicited by Akt2 in LSCC have not been elucidated. Here, we transfected a CRC cell line HCT116 with Akt-2 targeted shRNA in order to establish a cell line with Akt2 knockdown. In vitro experiments showed that knockdown Akt2 in HCT116 cells was associated with decrease in cell proliferation as well as enhanced cell apoptosis. Furthermore, our results demonstrated that Akt2 knockdown correlated with elevated chemosensitivity of HCT116 cells to paclitaxel. Importantly, we found that knockdown of AKt2 resulted in downregulation of MDR-1 and MRP-1. Our findings may lead to a better understanding of the biological effect of Akt2 and may provide mechanistic insights for developing potential therapeutic strategies targeting AKt2.

The purpose of this study is to investigate the protective effect of gambogenic acid (GA) in acetaminophen (APAP)-induced hepatotoxicity in rat models. GA (10 mg/kg) was administered intraperitoneal (i.p.) to rats for 7 consecutive days followed by APAP (500 mg/kg) single dose (i.p.) on the final day after GA administration. The levels of MDA, GSH, SOD, CAT, GPx, GST, ALP, AST, ALT, proinflammatory cytokines (TNF-α, IL-1β, IL-6), apoptosis markers (caspase-3 and -9, Bax, Bcl-2), 4-hydroxynonenal (4-HNE), and prostaglandin E2 (PGE2) were evaluated. Results exhibited protective effects of GA by inhibiting inflammation, preventing oxidative stress and apoptosis in APAP-induced liver. Histopathological changes caused by APAP were attenuated, protein expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were upregulated, and nuclear factor–kappa β (NF-kβ) was downregulated by GA. In summary, GA significantly exerted anti-inflammatory and antiapoptotic effects against APAP-induced hepatotoxicity potentially through regulation of PI3K/Akt and NF-kβ signaling pathways.