| Acetyl-11-keto-beta-boswellicacid (AKBA) is the derivative of boswellic acids that are the effective components of gum resin of Boswellia serrata. AKBA has been considered to be effective in some chronic inflammation diseases and cancers. In this study, we evaluated the activity of AKBA on the growth of human gastric carcinomas both in vitro and in vivo studies. In vitro assay, we performed the experiments of CCK-R and clonogenic formation to determine the inhibitory effect of AKBA on cancer growth. A xenograft-nude mouse model was employed to evaluate the efficacy of AKBA in animal bearing SGC-7901cells. AKBA by oral administration significantly delayed the growth of SGC-7901xenografts with no loss of body weight. The inhibitory effect of AKBA might due to its ability in the induction of apoptosis, showing the apoptotic characteristics in morphology, the increase of Annexin-V/FITC and propidium iodide (PI) staining cells and DNA ladder in cancer cells. The apoptotic effect of AKBA was also observed in SGC-7901xenografts, showing the increase of TUNEL staining cells. Western blotting indicated an increase of cleaved caspase-9,-3, cleaved PARP and Bax/Bcl-2ratio in the AKBA-treated cancer cells. Further analysis showed that AKBA inhibited the expressions of (3-catenin and GSK3β, the important molecules of the Wnt/β-catenin signaling pathway, and its targets, cyclin D1, PCNA, survivin, c-Myc, MMP-2and MMP-7in SGC-7901cells. These results suggested that AKBA inhibited the growth of gastric carcinoma and induced cancer cells to apoptosis through the mechanism of down-regulation of the Wnt/β-catenin signaling pathway. AKBA could be use as an adjuvant agent for treatment of gastric carcinomas. |
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