Hillman G G, Forman J D, Kucuk O, Yudelev M, Maughan R L, Rubio J, Layer A, Tekyi-Mensah S, Abrams J, Sarkar F H
Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, and Harper Hospital, Detroit, Michigan 48201, USA.
Clin Cancer Res. 2001 Feb;7(2):382-90.
We have shown previously that genistein, the major isoflavone in soybean, inhibited the growth of human prostate cancer cells in vitro by affecting the cell cycle and inducing apoptosis. To augment the effect of radiation for prostate carcinoma, we have now tested the combination of genistein with photon and neutron radiation on prostate carcinoma cells in vitro. The effects of photon or neutron radiation alone or genistein alone or both combined were evaluated on DNA synthesis, cell growth, and cell ability to form colonies. We found that neutrons were more effective than photons for the killing of prostate carcinoma cells in vitro, resulting in a relative biological effectiveness of 2.6 when compared with photons. Genistein at 15 microM caused a significant inhibition in DNA synthesis, cell growth, and colony formation in the range of 40-60% and potentiated the effect of low doses of 200-300 cGy photon or 100-150 cGy neutron radiation. The effect of the combined treatment was more pronounced than with genistein or radiation alone. Our data indicate that genistein combined with radiation inhibits DNA synthesis, resulting in inhibition of cell division and growth. Genistein can augment the effect of neutrons at doses approximately 2-fold lower than photon doses required to observe the same efficacy. These studies suggest a potential of combining genistein with radiation for the treatment of localized prostate carcinoma.
我们之前已经表明,大豆中的主要异黄酮染料木黄酮通过影响细胞周期和诱导凋亡在体外抑制人前列腺癌细胞的生长。为了增强前列腺癌放疗的效果,我们现在在体外测试了染料木黄酮与光子和中子辐射联合对前列腺癌细胞的作用。评估了单独光子或中子辐射、单独染料木黄酮或两者联合对DNA合成、细胞生长以及细胞形成集落能力的影响。我们发现,在体外中子对前列腺癌细胞的杀伤比光子更有效,与光子相比相对生物效应为2.6。15微摩尔的染料木黄酮在40 - 60%的范围内对DNA合成、细胞生长和集落形成产生显著抑制,并增强低剂量200 - 300厘戈瑞光子或100 - 150厘戈瑞中子辐射的效果。联合治疗的效果比单独使用染料木黄酮或辐射更显著。我们的数据表明,染料木黄酮与辐射联合抑制DNA合成,导致细胞分裂和生长受到抑制。与观察到相同疗效所需的光子剂量相比,染料木黄酮能在大约低2倍的剂量下增强中子的效果。这些研究表明染料木黄酮与辐射联合治疗局限性前列腺癌具有潜力。