Open AccessTumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC
Author(s) -
Tengfei Fan,
LinLin Bu,
Weiming Wang,
SiRui Ma,
Jian-Feng Liu,
WeiWei Deng,
Liang Mao,
GuangTao Yu,
Cong-Fa Huang,
Bing Liu,
Wenfeng Zhang,
ZhiJun Sun
Publication year - 2015
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.6294
Subject(s) - autophagy , stat3 , apoptosis , pi3k/akt/mtor pathway , cancer research , protein kinase b , carcinogenesis , medicine , stat protein , head and neck squamous cell carcinoma , cancer , chemistry , head and neck cancer , biochemistry
Autophagy is considered as a double-edged sword. It can prolong the survival of cancer cells and enhance its resistance to apoptosis, and paradoxically, defective autophagy has been linked to increased tumorigenesis, but the mechanism behind this phenomenon is unclear. In this study, we demonstrated that decreased phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) was correlated with increased autophagy through the Akt/mTOR and Erk signaling pathways in human head and neck squamous cell carcinoma (HNSCC). We also showed that blockage of STAT3 by NSC74859 could markedly induce apoptotic cell death and autophagy. Meanwhile, increased autophagy inhibited apoptosis. The pharmacological or genetic inhibition of autophagy and STAT3 further sensitized HNSCC cells to apoptosis. Furthermore, evidence from xenograft model proved that suppressed STAT3 activity combined with inhibition of autophagy promoted tumor regression better than either treatment alone. Taken together, this present study demonstrated that autophagy alleviates apoptotic cell death in HNSCC, and combination of inhibition of STAT3 by NSC74859 and autophagy might be a promising new therapeutic strategy for HNSCC.