Gumireddy Kiranmai, Li Anping, Cao Lili, Yan Jinchun, Liu Lin, Xu Xiaowei, Pazoles Christopher, Huang Qihong
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA ; Central labortary, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P. R. China.
J Carcinog Mutagen. 2013 Apr 30;2013. doi: 10.4172/2157-2518.S7-002.
Metastasis is the major cause of death in cancer. Most therapies currently in the clinic aim to eradicate primary tumor, but do not have ideal effects on metastasis. The lack of effective therapy in metastasis prevention and treatment results in high mortality rate in cancer patients with advanced diseases. Here we report the oxidized glutathione small molecule compound NOV-002 reduces cancer cell invasion and metastasis in an animal model in combination with chemotherapy drug gemcitabine. NOV-002 regulates cell signaling pathways by suppressing ErbB2 and PI3K phosphorylation and subsequent inhibition of Akt and RhoA activation. Our results suggest that NOV-002 affects cell signaling pathways that are critical for invasion and metastasis and can potentially be effective in metastasis treatment in combination of other chemotherapies.
转移是癌症患者死亡的主要原因。目前临床上的大多数治疗方法旨在根除原发性肿瘤,但对转移没有理想的效果。在转移性癌症的预防和治疗中缺乏有效的治疗方法,导致晚期癌症患者的死亡率很高。在此,我们报告氧化型谷胱甘肽小分子化合物NOV-002与化疗药物吉西他滨联合使用可在动物模型中降低癌细胞的侵袭和转移能力。NOV-002通过抑制ErbB2和PI3K磷酸化以及随后抑制Akt和RhoA激活来调节细胞信号通路。我们的结果表明,NOV-002影响对侵袭和转移至关重要的细胞信号通路,并可能在与其他化疗联合使用时对转移治疗有效。