三萜系化合物CDDO（2cyano3，12dioxooleana1，9dien28oic acid）和它的衍生物CDDOIm在nmol浓度下，可以增加TGFβ依赖的基因表达，譬如血纤维蛋白溶酶原激活剂的抑制剂1和TβRII，它们能够延长Smad2的活性，显著增加Smad3激活Smad结合元件CAGA荧光素酶的能力，它们还能够逆转Smad7的抑制活性，CDDO 和 CDDOIm还能增强actin和BMP的信号路径。增强转录共激活子p300CBP相关因子的表达，同TGFβ具有协同作用，这对于治疗TGFβ异常的疾病具有重要应用前景［22］。
2.2 针对Smad4基因开展的肿瘤基因治疗
TGFβ能够抑制正常上皮细胞的增殖，但肿瘤细胞却能频繁的产生抗性，正是由于Smad4作为肿瘤抑制基因频繁地在肿瘤中失活，恢复Smad4基因的功能目前已经成为肿瘤基因治疗的热点。
在裸鼠中，Smad4在结肠癌和胰腺癌中的表达能够抑制肿瘤生长。Smad4功能的恢复影响了血管生成，降低了血管内皮生长因子的表达，增加了血小板反应素1的表达。通过Smad4来调控肿瘤血管生成开关可以作为肿瘤抑制的一种新方法［23］。在Smad4缺失的胰腺癌CFPac1 细胞中，利用腺病毒过表达Smad4基因，可以降低铆定不依赖生长超过50%，抑制异种肿瘤生长［24］。
用重组腺病毒载体将Smad4基因转染到Smad4缺失的乳腺癌细胞MDAMB468中，TGFβ信号恢复了血纤维蛋白溶酶原激活剂的抑制剂1和p21基因的表达，Smad4表达的细胞在S期适度缩短，但没有诱导凋亡。而Smad4表达的细胞分散生长，悬浮培养的时候，能迅速失巢凋亡（anoikis）。进一步说明Smad4的缺失与肿瘤的恶变存在着紧密的相关性［25］。
肿瘤的发生是一个多基因，多途径相互作用的过程，TGF/Smads信号通路的异常是肿瘤的发生发展以及肿瘤的浸润和转移的重要因素，因此研究TGFβ信号转导与肿瘤的关系，对于阐明肿瘤的发病机理和肿瘤的治疗与预后都有重要的意义。
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