Cancer Research, 2005, 65(8):3396-403.

Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model

Sharon A. Vantyghem, Ann F. Chambers, et al

Departments of Pathology and Oncology, University of Western Ontario; and London Regional Cancer Centre and London Health Sciences Centre, London, Ontario, Canada

Metastatic spread, not primary tumor burden, is the leading cause of breast cancer deaths. For patient prognosis to improve, new systemic adjuvant therapies that are capable of effectively inhibiting the outgrowth of seeded tumor cells after surgical treatment of the primary breast tumor are needed. To facilitate the preclinical development of such therapies, relevant animal models of breast cancer metastasis that can mimic the postsurgical adjuvant setting are required. Here we developed a preclinical xenograft model of breast cancer metastasis where the primary tumor was removed by surgical resection before systemic adjuvant treatment. We used this model to assess the antimetastatic effect of postsurgical dietary intervention with the soy isoflavone genistein. The anticancer activity of genistein has been established in vitro and in vivo, however, few studies have tested the potential of genistein as an antimetastatic therapy. Using our model, we tested the efficacy of adjuvant treatment with genistein to inhibit the outgrowth of metastases postsurgery. To establish primary tumors, human breast carcinoma cells, MDA-MB-435/HAL, were implanted into the mammary fat pad of female nude mice. Primary tumors were left to grow for 5 weeks before being surgically removed. Mice were then randomized into two diet groups: control soy-free diet versus genistein-supplemented diet. Five weeks later, metastatic burden was assessed. Genistein reduced the percent metastatic burden in the lungs by 10-fold. These results indicate that dietary intervention following cancer surgery can affect the outgrowth of seeded tumor cells. The availability of well-characterized, clinically relevant animal models for studying factors that regulate metastatic outgrowth postsurgery will provide an important tool for developing new systemic adjuvant therapies.

美国《癌症研究》，2005年

饮食金雀异黄素在术后原位乳腺癌模型中降低转移几率

莎朗 A 万蒂格，安 F 钱伯斯，等

西安大略大学病理与肿瘤学系; 和伦敦地区癌症中心和伦敦健康科学中心，伦敦，安大略省，加拿大

转移性扩散，而不是原发性肿瘤负担，是导致乳腺癌死亡的主要原因。对于患者预后的改善，新的系统性辅助治疗能够有效地抑制原发性乳腺手术治疗后的种子肿瘤细胞的生长需要肿瘤为了促进临床前发展这样的疗法，乳腺癌转移的相关动物模型可以模拟术后辅助设置是必需的。在这里我们开发了乳腺癌转移的临床前异种移植模型在全身辅助治疗前通过手术切除原发性肿瘤。我们使用这个模型来评估抗转移作用用大豆异黄酮染料木素进行术后饮食干预。染料木素的抗癌活性已在体外和体内建立，然而，很少有研究测试了染料木素作为抗转移治疗的潜力。使用我们的模型，我们测试了佐剂的功效用染料木素处理以抑制转移瘤的外生生长。为了建立原发性肿瘤，人乳腺癌细胞，将MDA-MB-435 / HAL植入雌性裸鼠的乳腺脂肪垫中。原发性肿瘤在生长前5周生长手术切除。然后将小鼠随机分为两个饮食组：控制无大豆饮食和补充维生素A的饮食。五周后，评估转移性负担。染料木黄酮将肺转移的百分比降低10倍。这些结果表明饮食癌症手术后的干预可影响种子肿瘤细胞的生长。具有良好表征的临床相关性用于研究调节转移性外生生长因子的动物模型将为开发新的系统性提供重要的工具辅助疗法。