Journal
JOURNAL OF CANCER
Volume 11, Issue 3, Pages 570-582Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.35631
Keywords
IL-6/STAT3 signaling; HCC; TACE; HIF-1 alpha; SNAI1
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Funding
- National Natural Scientific Foundation of China [81301743, 81572733, 81272645, 81572847]
- New Medicine Research Project from THE First Hospital of Xian Jiaotong University [XJTU1AF-CRF-2016-002]
- Research Fund for the doctoral Program of High Education of China from Ministry of Education [20120201120090]
- Key Science and Technology Program of Shaanxi Province [2016SF-206]
- Fundamental Research Funds for the Basic Research Operating expenses Program of Central College - Xi'an Jiaotong University
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Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma according to BCLC algorithm. However, it has been unclear about the TACE-related predictive bio-markers and underlying molecular mechanisms. This investigation revealed that HCCs with higher HIF-1 alpha suffered from unfavorable OS after TACE. mRNA expression microarray revealed that HIF-1 alpha was potential target of p-STAT3 which was verified by ChIP and immunoblotting assay. Activation of IL-6/STAT3/HIF-1 alpha signaling was found to promote EMT and chemoresistance to Doxorubicin in vitro and in vivo by regulating SNAI1. Hypoxia did not enhance HIF-1 alpha expression and influence cell growth and chemoresistence to Doxorubicin in HCC cells when STAT3 expression was abolished. Taken together, HIF-1 alpha overexpression in HCC tissues predicted the unfavorable outcome of HCCs after TACE and IL-6/STAT3 pathway resulted in EMT induced-metastases and chemoresistance of HCC after TACE through HIF-1 alpha/SNAI1 axis.
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