ASIA unversity:Item 310904400/79914
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    题名: CTGF increases drug resistance to paclitaxel by upregulating survivin expression in human osteosarcoma cells
    作者: Ts, Hsiao-Chi;Tsai, Hsiao-Chi;Hua, Chun-Yin;Huang, Chun-Yin;Su, Hong-Lin;Su, Hong-Lin;湯智昕;Chih-Hsin, Tang *
    贡献者: 生物科技學系
    关键词: Osteosarcoma;Survivin;CTGF;Chemotherapy;Paclitaxel
    日期: 2014-05
    上传时间: 2014-07-03 15:42:45 (UTC+8)
    摘要: Osteosarcoma is the most common primary malignant tumor, and its treatments require more effective therapeutic approaches. Paclitaxel has a broad range of antitumor activities, including apoptosis-inducing effects. However, the majority of tumors in patients with advanced cancer eventually develop chemoresistance. Connective tissue growth factor (CTGF) is a secreted protein that modulates the invasiveness of certain human cancer cells by binding to integrins. However, the effect of CTGF in paclitaxel-mediated chemotherapy is unknown. Here, we report that the expression of CTGF in osteosarcoma patients was significantly higher than that of the CTGF expression in normal bone tissues. Overexpression of CTGF increased the resistance to paclitaxel-mediated cell apoptosis. In contrast, knockdown of CTGF expression by CTGF shRNA increased the chemotherapeutic effect of paclitaxel. In addition, CTGF increased resistance to paclitaxel-induced apoptosis through upregulation of survivin expression. Moreover, the AMP-activated protein kinase (AMPK)-dependent nuclear factor kappa B (NF-κB) pathway mediated paclitaxel-increased chemoresistance and survivin expression. In a mouse xenograft model, overexpression of CTGF promoted resistance to paclitaxel. In contrast, knockdown of CTGF expression increased the therapeutic effect of paclitaxel in this model. In conclusion, our data indicate that CTGF might be a critical oncogene of human osteosarcoma involved in resistance to paclitaxel treatment.
    显示于类别:[生物科技學系] 期刊論文


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