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首页> 外文期刊>Biochimica et Biophysica Acta. General Subjects >Acetyl-11-keto-β-boswellic acid (AKBA) inhibits human gastric carcinoma growth through modulation of the Wnt/β-catenin signaling pathway
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Acetyl-11-keto-β-boswellic acid (AKBA) inhibits human gastric carcinoma growth through modulation of the Wnt/β-catenin signaling pathway

机译：乙酰基十一酮-β-乳香酸（AKBA）通过调节Wnt /β-catenin信号通路抑制人胃癌的生长

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Background Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, an active component of Boswellia serrata gum resin. We examined the effect of AKBA on human gastric carcinoma growth and explored the underlying molecular mechanisms. Methods Inhibition of cancer cell growth was estimated by colorimetric and clonogenic assays. Cell cycle distribution was analyzed by flow cytometry and apoptosis determined using Annexin V-FITC/PI staining and DNA ladder quantification. After three weeks of oral AKBA administration in nude mice bearing cancer xenografts, animals were sacrificed and xenografts removed for TUNEL staining and western blot analysis. Results AKBA exhibited anti-cancer activity in vitro and in vivo. With oral application in mice, AKBA significantly inhibited SGC-7901 and MKN-45 xenografts without toxicity. This effect might be associated with its roles in cell cycle arrest and apoptosis induction. The results also showed activation of p21Waf1/Cip1 and p53 in mitochondria and increased cleaved caspase-9, caspase-3, and PARP and Bax/Bcl-2 ratio after AKBA treatment. Further analysis suggested that these effects might arise from AKBA's modulation of the aberrant Wnt/β-catenin signaling pathway. Upon AKBA treatment, β-catenin expression in nuclei was inhibited, and membrane β-catenin was activated. In the same sample, active GSK3β was increased and its non-active form decreased. Levels of cyclin D1, PCNA, survivin, c-Myc, MMP-2, and MMP-7, downstream targets of Wnt/β-catenin, were inhibited. Conclusions AKBA effects on human gastric carcinoma growth were associated with its activity in modulating the Wnt/β-catenin signaling pathway. General significance AKBA could be useful in the treatment of gastric cancers.
机译：背景乙酰基-11-酮基-β-乳香酸（AKBA）是乳香的一种衍生物，是乳香锯缘青蟹胶树脂的活性成分。我们检查了AKBA对人胃癌生长的影响，并探讨了潜在的分子机制。方法通过比色法和克隆形成法评估对癌细胞生长的抑制作用。通过流式细胞术分析细胞周期分布，并使用膜联蛋白V-FITC / PI染色和DNA阶梯定量确定细胞凋亡。在携带癌异种移植物的裸鼠中口服AKBA 3周后，处死动物并取出异种移植物进行TUNEL染色和蛋白质印迹分析。结果AKBA在体外和体内均表现出抗癌活性。通过在小鼠中口服应用，AKBA可以显着抑制SGC-7901和MKN-45异种移植而无毒性。这种作用可能与其在细胞周期停滞和凋亡诱导中的作用有关。结果还显示，AKBA处理后，线粒体中p21Waf1 / Cip1和p53的激活和裂解的caspase-9，caspase-3以及PARP和Bax / Bcl-2比率增加。进一步的分析表明，这些影响可能是由AKBA对异常Wnt /β-catenin信号通路的调节引起的。 AKBA处理后，细胞核中的β-catenin表达受到抑制，β-catenin膜被激活。在同一样品中，活性GSK3β增加而其非活性形式减少。 Wnt /β-catenin的下游目标细胞周期蛋白D1，PCNA，存活蛋白，c-Myc，MMP-2和MMP-7的水平受到抑制。结论AKBA对人胃癌生长的影响与其在调节Wnt /β-catenin信号通路中的活性有关。一般意义AKBA可用于治疗胃癌。

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