| RRC ID |
69319
|
| 著者 |
Zhang S, Tang W, Weng S, Liu X, Rao B, Gu J, Chen S, Wang Q, Shen X, Xue R, Dong L.
|
| タイトル |
Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma.
|
| ジャーナル |
Oncotarget
|
| Abstract |
Patients with esophageal squamous cell carcinoma (ESCC) are often diagnosed with advanced diseases that respond poorly to chemotherapy. Here we reported that Apollon, a membrane-associated inhibitor of apoptosis protein, was overexpressed in ESCC cell lines and clinical ESCC tissues, and Apollon overexpression clinically correlated with poor response to chemotherapy (P = 0.001), and short overall survival (P = 0.021). Apollon knockdown increased cisplatin/docetaxel-induced apoptosis, mitochondrial dysfunction and cytochrome c release in two ESCC cell lines. Apollon knockdown potentiated cisplatin/docetaxel-induced long-term cell growth inhibition, and enhanced chemosensitivity of ESCC cells to cisplatin/docetaxel in xenograft tumor models. Apollon knockdown also enhanced cisplatin/docetaxel-induced activation of caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) in ESCC cells and xenograft tumor models. Mechanism studies revealed that the effect of Apollon on chemosensitivity is mainly mediated by Smac. Apollon expression strongly and negatively correlated with Smac expression in clinical ESCC tissues (P = 0.001). Apollon targeted Smac for degradation in ESCC cells. The effect of Apollon on chemosensitivity was reversed by Smac knockdown in ESCC cells. Taken together, our data show association of Apollon expression with chemotherapeutic response in ESCC, and provide a strong rationale for combining Apollon antagonism with chemotherapy to treat ESCC.
|
| 巻・号 |
5(16)
|
| ページ |
7183-97
|
| 公開日 |
2014-8-30
|
| DOI |
10.18632/oncotarget.2293
|
| PII |
2293
|
| PMID |
25216531
|
| PMC |
PMC4196194
|
| MeSH |
Animals
Apoptosis / physiology
Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cell Proliferation / physiology
Down-Regulation
Esophageal Neoplasms / drug therapy*
Esophageal Neoplasms / genetics
Esophageal Neoplasms / metabolism*
Esophageal Neoplasms / pathology
Esophageal Squamous Cell Carcinoma
Humans
Inhibitor of Apoptosis Proteins / biosynthesis*
Inhibitor of Apoptosis Proteins / genetics
Inhibitor of Apoptosis Proteins / metabolism
Male
Mice
Mice, Inbred BALB C
Middle Aged
Xenograft Model Antitumor Assays
|
| IF |
5.168
|
| リソース情報 |
| ヒト・動物細胞 |
TE-4(RCB2097)
TE-5(RCB1949)
TE-8(RCB2098) |
