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Sorafenib with ASC‐J9 ® synergistically suppresses the HCC progression via altering the pSTAT3‐CCL2/Bcl2 signals
Author(s) -
Xu Junjie,
Lin Hui,
Li Gonghui,
Sun Yin,
Shi Liang,
Ma WenLung,
Chen Jiang,
Cai Xiujun,
Chang Chawnshang
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30446
Subject(s) - sorafenib , cancer research , hepatocellular carcinoma , stat3 , apoptosis , medicine , oncology , biology , biochemistry
Sorafenib is currently used as a standard treatment to suppress the progression of hepatocellular carcinoma (HCC), especially in advanced stages. However, patients who receive Sorafenib treatment eventually develop resistance without clear mechanisms. There is a great need for better efficacy of Sorafenib treatment in combination with other therapies. Here, we demonstrated that the treatment combining Sorafenib with ASC‐J9 ® could synergistically suppress HCC progression via altering cell‐cycle regulation, apoptosis and invasion. Mechanism dissection suggests that while Sorafenib impacts little or even slightly increases the activated/phosphorylated STAT3 (p‐STAT3), a key stimulator to promote the HCC progression, adding ASC‐J9 ® significantly suppresses the p‐STAT3 expression and its downstream genes including CCL2 and Bcl2. Interrupting these signals via constitutively active STAT3 partially reverses the synergistic suppression of Sorafenib‐ASC‐J9 ® combination on HCC progression. In vivo studies further confirmed the synergistic effect of Sorafenib‐ASC‐J9 ® combination. Together, these results suggest the newly developed Sorafenib‐ASC‐J9 ® combination is a novel therapy to better suppress HCC progression.