PI3-kinase 抑制作用协同增强了羽扇醇在肝癌中的抗肿瘤作用。
PI3-kinase inhibition synergistically promoted the anti-tumor effect of lupeol in hepatocellular carcinoma.
机构信息
Laboratory of Cellular and Molecular Tumor Immunology, Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, P, R, China.
出版信息
Cancer Cell Int. 2013 Nov 1;13(1):108. doi: 10.1186/1475-2867-13-108.
BACKGROUND
Lup-20(29)-en-3H-ol (Lupeol), a dietary triterpene, has been shown to possess multiple pharmacological activities including anti-tumor effects
METHODS
In the current study, we noted that low doses of lupeol (<40 μM) promoted the growth of hepatocellular carcinoma (HCC) cells with a significant activation of the PI3-kinase/Akt signaling pathway. We further investigated the combined anti-tumor effect of lupeol and S14161, a newly identified PI3-Kinase inhibitor in vitro and in vivo
RESULTS
The results demonstrated that lupeol and S14161 could exert a synergistic antitumor effect resulting in chemo-sensitization of HCC to low doses of lupeol. Using an in vivo HCC model, we further demonstrated that lupeol and S14161 synergistically inhibited tumor growth without any adverse effects on body weight
CONCLUSION
Our studies showed that the activation of PI3-kinase/Akt pathway resulted in the tumor-promoting effect with low doses of lupeol. Combining PI3-kinase inhibitor with lupeol could synergistically augment the anti-tumor effect of lupeol and might be an applicable strategy for HCC therapy.
背景
Lup-20(29)-en-3H-ol（羽扇豆醇），一种膳食三萜，已被证明具有多种药理活性，包括抗肿瘤作用。
方法
在本研究中，我们注意到低剂量的羽扇醇（<40 μM）可促进肝癌（HCC）细胞的生长，同时显著激活 PI3-激酶/Akt 信号通路。我们进一步研究了羽扇醇和 S14161 的联合抗肿瘤作用，S14161 是一种新鉴定的 PI3-激酶抑制剂，在体外和体内均有研究。
结果
结果表明，羽扇醇和 S14161 可发挥协同抗肿瘤作用，使 HCC 对低剂量羽扇醇产生化疗敏感性。通过体内 HCC 模型，我们进一步证明，羽扇醇和 S14161 协同抑制肿瘤生长，而对体重无任何不良影响。
结论
我们的研究表明，PI3-激酶/Akt 通路的激活导致低剂量羽扇醇的肿瘤促进作用。将 PI3-激酶抑制剂与羽扇醇联合使用可以协同增强羽扇醇的抗肿瘤作用，可能是 HCC 治疗的一种适用策略。
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