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https://ir.cnu.edu.tw/handle/310902800/32164
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| 標題: | Bortezomib enhances radiosensitivity in oral cancer through inducing autophagy-mediated TRAF6 oncoprotein degradation |
| 作者: | Wu, Yuan-Hua
Wu, Wun-Syuan
Lin, Li-Ching
Liu, Chiang-Shin
Ho, Sheng-Yow
Wang, Bour-Jr
Huang, Bu-Miin
Yeh, Ya-Ling
Chiu, Hui-Wen
Yang, Wei-Lei
Wang, Ying-Jan |
| 貢獻者: | Natl Cheng Kung Univ, Dept Environm & Occupat Hlth, Coll Med
Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Radiat Oncol, Coll Med
Chi Mei Med Ctr, Dept Radiat Oncol
Taipei Med Univ, Sch Med
Chung Hwa Univ Med Technol
Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Pathol, Coll Med
Chi Mei Med Ctr, Dept Radiat Oncol
Chang Jung Christian Univ
Natl Cheng Kung Univ Hosp, Dept Occupat & Environm Med
Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
Chia Nan Univ Pharm & Sci, Inst Cosmet Sci
Natl Cheng Kung Univ, Coll Med, Dept Cell Biol & Anat
Taipei Med Univ, Grad Inst Clin Med, Coll Med
Taipei Med Univ, Shuang Ho Hosp, Dept Internal Med, Div Nephrol
Univ Texas MD Anderson Canc Ctr
Asia Univ, Dept Biomed Informat
China Med Univ, China Med Univ Hosp, Dept Med Res |
| 關鍵字: | Oral squamous cell carcinoma
Radiation
TRAF6
Ubiquitination
Autophagy |
| 日期: | 2018-04-27 |
| 上傳時間: | 2019-11-15 15:43:23 (UTC+8) |
| 出版者: | BIOMED CENTRAL LTD |
| 摘要: | Background: Oral squamous cell carcinoma (OSCC) is a malignant tumor that may occur anywhere within the oral cavity. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. We investigated the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in OSCC cells treated with bortezomib (a proteasome inhibitor) combined with irradiation (IR) treatment. Methods: The effects of combined treatment in OSCC cells were investigated using assays of cell viability, autophagy, apoptosis, western blotting, and immunofluorescence staining. The ubiquitination of proteins was analyzed by immunoprecipitation. Stable knockdown of TRAF6 in OSCC cells was constructed with lentivirus. The xenograft murine models were used to observe tumor growth. Results: We found synergistic effects of bortezomib and IR on the viability of human oral cancer cells. The combination of bortezomib and IR treatment induced autophagic cell death. Furthermore, bortezomib inhibited IR-induced TRAF6 ubiquitination and inhibited TRAF6-mediated Akt activation. Bortezomib reduced TRAF6 protein expression through autophagy-mediated lysosomal degradation. TRAF6 played an oncogenic role in tumorigenesis of human oral cancer cells and oral tumor growth was suppressed by bortezomib and IR treatment. In addition, OSCC patients with expression of TRAF6 showed a trend towards poorer cancer-specific survival when compared with patients without TRAF6 expression. Conclusions: A combination of a proteasome inhibitor, IR treatment and TRAF6 inhibition could be a novel therapeutic strategy in OSCC. |
| link: | http://dx.doi.org/10.1186/s13046-018-0760-0 |
| 關聯: | Journal of Orthopaedic Surgery and Research, v.37, 91 |
| 顯示於類別: | [化妝品應用與管理系(所)] 期刊論文
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