Huang Jun, Chen Zhen-Hua, Ren Chun-Mei, Wang Dong-Xu, Yuan Shuang-Xue, Wu Qiu-Xiang, Chen Qian-Zhao, Zeng Yu-Hua, Shao Ying, Li Yang, Wu Ke, Yu Yu, Sun Wen-Juan, He Bai-Cheng
Oncol Rep. 2015 Dec;34(6):3203-11. doi: 10.3892/or.2015.4309.
Colon cancer is one of the most common malignancies. Although the current treatment regimes for colon cancer have been well-developed in the past decades, the prognosis remains still undesirable. It is still urgent to explore new treatment strategies for colon cancer. Natural products is one of the most useful sources for anticancer agents, although some of them have serious side-effects. Evodiamine (Evo) is an quinolone alkaloid from the traditional herb medicine Evodia rutaecarpa. In the present study, we investigated the anticancer effect of Evo in human colon cancer cells. We found that Evo exhibits prominent antiproliferation and apoptosis inducing effects in LoVo cells. Evo leads to apparent downregulation of HIF-1α either in vitro or in vivo; exogenous expression of HIF-1α can attenuate the antiproliferation effect of Evo in LoVo cells, while HIF-1α knockdown potentiates this effect greatly. Further analysis indicated that Evo can also inhibit the phosphorylation of Akt1/2/3 and decrease greatly the expression of IGF-1. Thus, our findings strongly suggested that the anticancer effect of Evo in human colon cancer may be partly mediated by downregulating HIF-1α expression, which is initiated by inactivating PI3K/Akt signaling transduction though decreasing the expression of IGF-1 in colon cancer cells. Therefore, Evo may be used alone or in combination as a potential anticancer agent for colon cancer treatment.
结肠癌是最常见的恶性肿瘤之一。尽管在过去几十年中结肠癌的当前治疗方案已得到充分发展，但预后仍然不理想。探索结肠癌的新治疗策略仍然迫在眉睫。天然产物是抗癌药物最有用的来源之一，尽管其中一些有严重的副作用。吴茱萸碱（Evo）是一种来自传统草药吴茱萸的喹诺酮生物碱。在本研究中，我们研究了Evo对人结肠癌细胞的抗癌作用。我们发现Evo在LoVo细胞中表现出显著的抗增殖和诱导凋亡作用。Evo在体外或体内均可导致HIF-1α明显下调；HIF-1α的外源性表达可减弱Evo在LoVo细胞中的抗增殖作用，而HIF-1α基因敲低则可大大增强这种作用。进一步分析表明，Evo还可抑制Akt1/2/3的磷酸化并显著降低IGF-1的表达。因此，我们的研究结果强烈表明，Evo对人结肠癌的抗癌作用可能部分是通过下调HIF-1α表达介导的，这是通过降低结肠癌细胞中IGF-1的表达来使PI3K/Akt信号转导失活而引发的。因此，Evo可单独使用或联合用作结肠癌治疗的潜在抗癌药物。
