Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/95839
標題: TRIB3 downregulation enhances doxorubicin-induced cytotoxicity in gastric cancer cells
作者: Wu, I-Jung
Lin, Rong-Jaan
Wang, Hsin-Chiao
Yuan, Tein-Ming
莊秀美
Chuang, Show-Mei
關鍵字: Antibiotics, Antineoplastic
Apoptosis
Cell Cycle Proteins
Cell Line, Tumor
Down-Regulation
Doxorubicin
Gene Expression Regulation, Neoplastic
Humans
MAP Kinase Signaling System
Protein-Serine-Threonine Kinases
Repressor Proteins
Stomach
Stomach Neoplasms
出版社: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
摘要: TRIB3, which is a pseudokinase known to regulate multiple pro-survival pathways, appears to be a potential therapeutic target for the treatment of human tumors. However, its precise role in cancer is controversial, as TRIB3 protein levels have been associated with both good and poor prognosis in cancer patients. Here, we investigated the significance of TRIB3 expression in the survival of gastric cancer cells exposed to anticancer drugs. We found that the tested anticancer drug, doxorubicin, induced cytotoxicity by decreasing TRIB3 transcription, which was followed by apoptotic cell death. Moreover, TRIB3 siRNA knockdown appeared to enhance doxorubicin-induced apoptosis in gastric cancer cells, concurrently with altering the expression of downstream apoptotic factors. Conversely, overexpression of TRIB3 significantly protected cells against doxorubicin-induced apoptosis. Our results indicate that downregulation of TRIB3 appears to promote cell death and enhance doxorubicin-induced apoptosis, supporting the anti-apoptotic role of TRIB3. The inductions of three classes of MAPKs failed to affect doxorubicin-mediated TRIB3 downregulation, while TRIB3 overexpression did not affect doxorubicin-induced MAPK activation. In sum, our findings indicate that TRIB3 plays an anti-apoptotic role in doxorubicin-treated gastric cancer cell lines, perhaps indicating that the status of TRIB3 expression in response to anticancer drugs, such as doxorubicin, irinotecan or oxaliplatin, may reflect the efficiency for cancer therapy.
URI: http://hdl.handle.net/11455/95839
Appears in Collections:生醫工程研究所

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