期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 77, 期 -, 页码 108-113出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2015.12.010
关键词
MG132; Oral squamous cell carcinoma; X-box binding protein 1; Apoptosis; Silencing
资金
- Shandong Province Natural Science Foundation, China [ZR2013HL015, ZR2015HL093]
- National Natural Science Foundation of China [81272958, 81472530]
- Foundation for Outstanding Young Scientist of Shandong Province [BS2014YY054]
Background: Proteasome inhibitor Carbobenzoxy-Leu-Leu-leucinal (MG132) induces the unfolded protein response (UPR) in oral squamous cell carcinoma (OSCC). X-box binding protein 1 (XBP1) is a key UPR component that regulates endoplasmic reticulum stress (ER) homeostasis. This study was aimed to investigate the activation of IRE1 alpha-TRAF2-ASK1-JNK pathway by silencing the XBP1 expression in an OSCC cell line. Methods: The XBP1 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the Tca-8113 cells. The effect of XBP-1 gene silencing on IRE1 alpha-TRAF2-ASK1-JNK pathway under MG132 induced endoplasmic reticulum stress in Tca-8113 were investigated by real-time RT-PCR or western blot. Cell apoptosis was detected by flow cytometry. Results: XBP1 expression was reduced in transfected groups and MG132 groups. shRNA-XBP1 induces IRE1 alpha-TRAF2-ASK1 signaling activation to activate pro-apoptotic ASK1-JNK signaling. Moreover, combined shRNA-XBP1 with MG132 further enhanced downregulated XBP1 expression and upregulated activation of ASK1-JNK signaling. Conclusions: Silencing XBP1 expression under MG132 induced ER stress block the XBP1 survival pathway and synergism with MG132 to promote Tca8113 cell apoptosis. These findings provide a therapeutic option in oral squamous cell carcinoma by inhibition of proteasome and XBP1 splicing. (C) 2015 Elsevier Masson SAS. All rights reserved.
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