【转帖】Int J Oncol：类维生素A或可抑制乳腺癌恶化

zhulikou431

近日刊登在国际杂志International Journal of Oncology上的一篇报道指出，维生素A的衍生物，也就是常说的类维生素A，其在蕃薯和胡萝卜中水平较高，可以帮助将前癌症细胞转化成为健康的乳腺细胞，这或许可以帮助解释为何为何维生素A不能改变成熟的癌症细胞，而只能改变那种前癌细胞，而且仅仅是在一定的剂量范围内才可以发挥此功能。
研究者Sandra V. Fernandez表示，细胞在变成恶性之前会经历许多改变，文章中我们就利用一种乳腺癌模型来进行研究，这种模型包含有四种阶段的乳腺细胞，分别为正常细胞、前癌症细胞、癌性细胞以及完全恶性的癌细胞。
当研究者将这四种类型的细胞暴露于不同浓度的类维生素A中时，他们发现前癌性细胞发生了较大变化，前癌性细胞不仅开始变得和正常细胞相似，而且其遗传特性也变化地和正常细胞一样；这种前癌性细胞中443个基因发生了上调或者下调，都趋向于向恶性转变，但是在经过类维生素A处理后这些基因的表达都趋向于正常水平，这也就表明，类维生素A可以通过进行表观遗传学的修饰来促进癌细胞正常化。
Fernandez教授说道，我们后期将会进行深入研究，看看是否其可以应用于临床试验中；更有意思的是，完全癌性的细胞根本不会对类维生素A产生反应，这就表明类维生素A或许仅仅对抑制癌症恶化起作用。
另外研究者表示只有一种浓度的类维生素A具有抗癌效应，下一步研究者将检测类维生素A的最佳含量是否可以在动物模型中维持，以及是否可以应用里临床研究中。


All trans-retinoic acid (ATRA) induces re-differentiation of early transformed breast epithelial cells
Maria F. Arisi, Rebecca A. Starker, Sankar Addya, Yong Huang, Sandra V. Fernandez
Retinoids have been used as potential chemotherapeutic or chemopreventive agents because of their differentiative, anti-proliferative, pro-apoptotic and antioxidant properties. We investigated the effect of all trans-retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the MCF-10F human normal breast epithelial cells with high dose of estradiol and consists of four cell lines which show a progressive neoplastic transformation: MCF-10F, normal stage; trMCF, transformed MCF-10F; bsMCF, invasive stage; and caMCF, tumorigenic stage. In 3D cultures, MCF-10F cells form tubules resembling the structures in the normal mammary gland. After treatment with estradiol, these cells formed tubules and spherical masses which are indicative of transformation. Cells that only formed spherical masses in collagen were isolated (trMCF clone 11) and treated with ATRA. After treatment with 10 or 1 μM ATRA, the trMCF clone 11 cells showed tubules in collagen; 10 and 43% of the structures were tubules in cells treated with 10 and 1 μM ATRA, respectively. Gene expression studies showed that 207 genes upregulated in transformed trMCF clone 11 cells were downregulated after 1 μM ATRA treatment to levels comparable to those found in the normal breast epithelial cells MCF-10F. Furthermore, 236 genes that were downregulated in trMCF clone 11 were upregulated after 1 μM ATRA treatment to similar levels shown in normal epithelial cells. These 443 genes defined a signature of the ATRA re-programming effect. Our results showed that 1 μM ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process and antagonistically regulate breast cancer associated genes. The invasive and tumorigenic cells did not show any changes in morphology after ATRA treatment. These results suggest that ATRA could be used as a chemopreventive agent to inhibit the progression of premalignant lesions of the breast.