Title:Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Volume: 12
Issue: 5
Author(s): Chengzhen Liang, Hao Li, Chengchun Shen, Jianbo Lai, Zhongli Shi, Bing Liu and Hui-min Tao
Affiliation:
Keywords:
Akt, Apoptosis, Gemcitabine, Genistein, NF-κB, Osteosarcoma, Immunoblotting, Electron Microscopy, Xenograft, Electrophoretic, Immunohistochemistry
Abstract: Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we
investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human
osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the
combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation
of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein
was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy
augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together,
these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the
chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma
treatment.
