期刊
PROTEOMICS
卷 13, 期 23-24, 页码 3411-3423出版社
WILEY-BLACKWELL
DOI: 10.1002/pmic.201300274
关键词
Apoptosis; Cell biology; Cervix cancer; Reticulum stress; Tanshinone IIA
资金
- National Science Council [NSC-99-2320-B-182-015-MY3]
- Chang Gung University [EMRPD1C0311]
- Chang Gung Memorial Hospital, Taiwan [CMRPD1B0401, CM-RPD1B0402, CMRPG891421]
Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC50 = 5.51 M) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP-homologous protein as well as apoptosis signal-regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial-related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.
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