生物体内的氧浓度被控制在一个很精确的范围内以保证体内多种生物化学反应的正常进行以及体内的氧化还原平衡。当外界氧环境发生变化时，例如在高原低氧条件下，生物体会对低氧环境做出反应，产生一系列适应低氧条件的新生蛋白质群，其中最重要的就是低氧诱导因子1（HIF-1，Hypoxia Inducible Factor-1）。HIF-1是由HIF-1α和HIF-1β两个亚基组成的异二聚体，两个亚基都是基础螺旋-环-螺旋-PAS真核转录因子超家族成员。HIF-1控制多个基因的表达，它们的蛋白产物对低氧条件有着灵敏的和长期的适应功能。这些蛋白的功能包括红细胞生成，糖酵解，促进细胞存活，抑制凋亡，抑制细胞分化和促进血管生成。HIF在肿瘤中经常过表达，尤其是HIF-1α在肿瘤中的上调已在多种癌症中得到证实。由于它的这些特性HIF已成为如今和未来癌症新药研究的重要靶位分子。本研究针对利用高通量筛选方法筛选出的一种潜在天然抗癌药物，HB99，对HIF-1α的抑制作用进行了验证，证实其能够降低HIF-1α的蛋白水平和转录活性。并初步探究了它作用于HIF-1α的分子机制，结果显示它对HIF-1α的转录有抑制作用，HIF-1α的mRNA水平比对照组下降了35%。同时发现HB99会下调细胞蛋白合成通路的激酶水平，这些可能是HIF-1α蛋白水平下降的原因。还进行了初步的细胞毒性实验，结果显示HB99对细胞的有杀伤作用，作用16小时大约杀死40%的细胞。为HB99作为抗癌药物的进一步研究和开发完成了一些初步工作。

In living organisms, oxygen concentration is controlled within a very narrow range to maintain the biochemical reactions and keep redox system is kept in equilibrium. When the level of oxygen in the environment changes, for example under highland low oxygen conditions on a plateau, organisms will respond to the low oxygen environment and produce a series of new proteins in order to adapt to the low oxygen conditions. Among these proteins, the most important is Hypoxia Inducible Factor-1 (HIF-1). HIF-1 is a heterodimer which is composed of HIF-1α and HIF-1β. These two subunits are both members of helix-loop-helix PER, ARNT, SIM (PAS) superfamily of eukaryotic transcription factors. HIF-1 controls the expression of many genes to adapt to hypoxia acutely and continuously. The functions of these proteins include erythrocytopoiesis, glycolysis, cell survival, anti-apoptosis and angiogenesis. HIF is overexpressed in cancer cells, especially, the up-regulation of HIF-1α is demonstrated in many kinds of tumors. Based on these facts, HIF is now considered as a key target of novel anti-cancer drugs.Here we studied a potential natural anticancer drug HB99 which was from the high throughput screen and verified a inhibitor against the transcriptional activity of HIF-1. HB99 reduces HIF-1 protein level and inhibits its transcriptional activity. We investigated the mechanism of the inhibition, it turned out that HB99 inhibit the transcription of HIF-1α, the amount of HIF-1α mRNA reduced 35% compare to control. HB99 decreases the kinase level in protein synthesis in cells. Then we tested the cytotoxicity of HB99, results showed that HB99 killed 40% of total cells after a 16 h treatment. Our results contributed a preliminary study for the future development on HB99 as an anticancer drug.