Wang Yu, Raffoul Julian J, Che Mingxin, Doerge Daniel R, Joiner Michael C, Kucuk Omer, Sarkar Fazlul H, Hillman Gilda G
Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA.
Radiat Res. 2006 Jul;166(1 Pt 1):73-80. doi: 10.1667/RR3590.1.
Pretreatment with genistein, a bioactive component of soy isoflavones, potentiated cell killing induced by radiation in human PC-3 prostate cancer cells in vitro. Using an orthotopic xenograft in nude mice, we demonstrated that genistein combined with prostate tumor irradiation caused greater inhibition of primary tumor growth and increased control of spontaneous metastasis to para-aortic lymph nodes, increasing mouse survival. Paradoxically, treatment with genistein alone increased metastasis to lymph nodes. This observation is of concern in relation to soy-based clinical trials for cancer patients. To address whether this observation is because nude mice have an impaired immune system, these studies were repeated in orthotopic RM-9 prostate tumors in syngeneic C57BL/6 mice. The combination of genistein with radiation in this model also caused a greater inhibition of primary tumor growth and spontaneous metastasis to regional para-aortic lymph nodes, whereas treatment with genistein alone showed a trend to increased lymph node metastasis. Data from the syngeneic and xenograft models are comparable and indicate that the combination of genistein with radiotherapy is more effective and safer for prostate cancer treatment than genistein alone, which promotes metastatic spread to regional lymph nodes.
染料木黄酮是大豆异黄酮的一种生物活性成分，体外实验中它预处理可增强辐射对人PC-3前列腺癌细胞的杀伤作用。利用裸鼠原位异种移植模型，我们证明染料木黄酮联合前列腺肿瘤放疗可更有效地抑制原发肿瘤生长，并增强对主动脉旁淋巴结自发转移的控制，从而提高小鼠生存率。矛盾的是，单独使用染料木黄酮治疗会增加淋巴结转移。这一观察结果与针对癌症患者的大豆相关临床试验有关。为了探究这一观察结果是否是因为裸鼠免疫系统受损，我们在同基因C57BL/6小鼠的原位RM-9前列腺肿瘤模型中重复了这些研究。在该模型中，染料木黄酮与放疗联合使用也能更有效地抑制原发肿瘤生长以及向主动脉旁区域淋巴结的自发转移，而单独使用染料木黄酮治疗则有增加淋巴结转移的趋势。同基因和异种移植模型的数据具有可比性，表明染料木黄酮与放疗联合治疗前列腺癌比单独使用染料木黄酮更有效、更安全，单独使用染料木黄酮会促进肿瘤向区域淋巴结的转移扩散。
