Cell Biochemistry and Biophysics, 2012, 62(1):177-84.

Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein

Ren Jie Zhou, Xue Qin Yang, Dong Wang, et al

Department of EmergencyXinqiao HospitalChongqingChina; Cancer Center, Research Institute of Surgery, Daping HospitalThird Military Medical UniversityChongqingPeople’s Republic of China

The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate cancer growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti-cancer effects by inhibiting protein tyrosine kinase that is involved in up-regulation of VEGF. We hypothesized that genistein, applied simultaneously with ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti-cancer effects of ATRA. The purpose of this study was to document potential synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We further explored the role of genistein on countering the ATRA-induced VEGF expression. We demonstrate that genistein enhances the ATRA-induced growth inhibition of A549 cells by promoting apoptosis. Further, the combined use of ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle phases. Finally, expression of VEGF (both mRNA and protein) was diminished in A549 cells exposed to both ATRA and genistein. In conclusion, our results demonstrate that genistein effectively enhances anti-cancer effects of ATRA, particularly, by countering the ATRA-induced up-regulation of VEGF. Our study provides an experimental basis for combined use of ATRA and genistein in the treatment of lung cancer.

美国《细胞生物化学与生物物理学》，2012年1月

染料木黄酮增强全反式维甲酸的抗肿瘤效果

周仁杰、 杨雪琴、 王东等

中国重庆新桥医院急症中心，第三军医大学大坪医院癌症中心

全反式维甲酸 (ATRA) 对癌症的作用复杂。ATRA 具有抗癌作用，因为它可以促进肿瘤细胞的分化。然而，ATRA 也上调了肿瘤细胞中血管内皮生长因子 (VEGF) 的表达，导致血管生成并因此促进癌细胞生长。染料木素，是一种关键的大豆非营养成分，通过抑制参与上调VEGF的蛋白酪氨酸激酶表现抗癌功效。我们假设金雀异黄素，与 ATRA同时应用，将抵消其不受欢迎的血管生成抑制作用，并因此增强 ATRA 的抗癌作用。本研究的目的是证明染料木黄酮和 ATRA对A549 肺腺癌细胞潜在的协同效应。我们进一步探究了染料木黄酮对逆转ATRA 诱导 的VEGF 表达的作用。我们证明染料木黄酮通过促进细胞凋亡，增强 ATRA 诱导A549 细胞的生长抑制作用。此外，联合使用 ATRA 和染料木黄酮会导致癌症细胞在 G0/G1 和 G2/M 期细胞周期阶段中止。最后，A549 细胞接触ATRA 和金雀异黄素后VEGF（mRNA 和蛋白）的表达减少。总之，我们的结果表明，染料木黄酮可以有效提高 ATRA的抗肿瘤作用，特别是，通过逆转 ATRA 诱导上调 VEGF 的表达。我们的研究为联合使用 ATRA 和染料木黄酮来治疗肺癌提供了实验依据。