Please use this identifier to cite or link to this item:
標題: CTGF increases drug resistance to paclitaxel by upregulating survivin expression in human osteosarcoma cells
作者: Tsai, Hsiao-Chi
Huang, Chun-Yin
Su, Hong-Lin
Tang, Chih-Hsin
關鍵字: CTGF;Chemotherapy;Osteosarcoma;Paclitaxel;Survivin;Animals;Antineoplastic Agents, Phytogenic;Cell Line, Tumor;Connective Tissue Growth Factor;Drug Resistance, Neoplasm;Humans;In Situ Nick-End Labeling;Inhibitor of Apoptosis Proteins;Mice;Mice, Nude;Osteosarcoma;Paclitaxel;Real-Time Polymerase Chain Reaction;Up-Regulation
Project: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1843, Issue 5, Page(s) 846-854.
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.
ISSN: 01674889
DOI: 10.1016/j.bbamcr.2014.01.007
Appears in Collections:生命科學系所

Show full item record

Google ScholarTM




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.