International Journal of Molecular Sciences, 2014, 15(3):3432-43.

Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

Weifeng Huang, Chunpeng Wan, Qicong Luo, et al

Department of Surgical Oncology, First Affiliated Hospital of Xiamen University & Xiamen Cancer Center, Xiamen 361003, Fujian, China; et al

Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer.

《国际分子科学杂志》，2014年2月

金雀异黄素抑制癌症干细胞的特性并减少胃癌的化疗抵抗性

黄伟锋、万春鹏、罗启聪等

中国福建厦厦门大学第一附属医院与癌症中心肿瘤外科等

金雀异黄素，是一种在大豆中发现的主要异黄酮，在体内和体外对许多不同的肿瘤类型具有抗癌效果。近年来越来越多的证据强力证明了在胃癌组织中的肿瘤干细胞的存在。在这里，我们发现低剂量的金雀异黄素 (15 µM)，提取自鸡血藤，通过集落形成法和肿瘤形成检测技术在两种类型的胃癌细胞中抑制了肿瘤细胞的自我更新能力。用金雀异黄素治疗胃癌细胞可以减少其对顺铂与 5-氟尿嘧啶 （氟尿嘧啶）的化疗耐药性。进一步的结果表明，减少化疗耐药可能与抑制 ABCG2 的表达和 ERK 1/2 的活性有关。此外，金雀异黄素在异种移植模型中降低了肿瘤重量。总之，金雀异黄素抑制了胃癌干细胞样属性并减少其化疗耐药。我们的研究结果为使用金雀异黄素改善胃癌患者的治疗提供了进一步的理论基础和实验依据。