Anti-Cancer Drugs, 2010, 21(3):288-96.

Enhanced anticancer effect of gemcitabine by genistein in osteosarcoma: the role of Akt and nuclear factor-κB

Bo Zhang, Zhong-Li Shi, Bing Liu, et al

Department of Orthopedics and Institute of Orthopedic Research, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cell lines. This study was designed to investigate whether combination therapy with gemcitabine and genistein enhances antitumor efficacy in osteosarcoma cell lines (MG-63 and U2OS). Our results show that significant reduction in cell viability and corresponding induction of apoptosis were observed with combination treatment in both cell lines. On the molecular level, we found that gemcitabine alone can activate nuclear factor κB (NF-κB) in osteosarcoma, suggesting the potential mechanism of acquired chemoresistance. In contrast, genistein reversed the cancer's resistance to gemcitabine through the downregulation of NF-κB activity and the suppression of Akt. These findings suggest that the combination of gemcitabine and genistein enhanced the antitumor efficacy by abrogating the Akt/NF-κB pathway. The marked ability to induce apoptosis with a combination of gemcitabine and genistein suggests that this could be a rational and novel approach for osteosarcoma preclinical and clinical trials.

英国《抗肿瘤药物》2010年3月

通过金雀异黄素增强吉西他滨对骨肉瘤的抗癌作用︰ Akt 和核因子 κ B 的作用

张博，石忠利，刘兵等

中国浙江大学医学院第二附属医院骨科和矫形外科研究院

金雀异黄素，一种无毒的黄酮类化合物，在多种肿瘤细胞具有强效的抗肿瘤作用。本研究旨在探讨金雀异黄素能否与吉西他滨联合治疗来增强对骨肉瘤细胞系 （MG-63和 U2OS） 的抗肿瘤效果。我们的研究结果显示在这两种细胞系可以观察到联合治疗能够显著减少细胞的活力并且诱导相应细胞凋亡。在分子水平上，我们发现单独的吉西他滨可以激活骨肉瘤中的核因子 κ B (NF-κ B)，展示了获得性耐药性的潜在机制。相比之下，染料木黄酮通过下调NF-κ B的 活性和抑制Akt来逆转癌症对吉西他滨的抵抗。这些发现表明吉西他滨和金雀异黄素的联合通过废除 Akt/NF-κ B的 通路来增强抗肿瘤的疗效。吉西他滨与金雀异黄素联合显著诱导细胞凋亡的能力表明这可能是一种合理而新颖的用于骨肉瘤的临床前和临床试验的方法。