EH-42: A Novel Small Molecule Induces Apoptosis and Inhibits Migration and Invasion of Human Hepatoma Cells through Suppressing STAT3 Signaling Pathway

Author(s): Qi-Zhe Gong, Di Xiao, Gui-Yi Gong, Jian Xu, Xiao-Dong Wen*, Feng Feng*, Wei Qu*.

Journal Name: Current Cancer Drug Targets

Volume 19 , Issue 7 , 2019

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Abstract:

Background: Since signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in hepatocellular carcinoma (HCC) and plays a key role in this tumor progression. Inhibition of the STAT3 signaling pathway has been considered as an effective therapeutic strategy for suppressing HCC development.

Objective: In this study, we investigated the anti-cancer effects of EH-42 on HCC cells and tried to explain the underlying mechanism.

Methods: MTT assay, colon formation assay and AnnexinV-FITC/PI double-staining assay were performed to assess the effects of EH-42 on cell growth and survival. Wound healing assay and transwell invasion assay were performed to assess the effects of EH-42 on cell migration and invasion. Western blotting assay was performed to analyze the effects of EH-42 on relative proteins.

Results: According to the MTT assay, colon formation assay and AnnexinV-FITC/PI doublestaining assay, EH-42 could suppress the growth and induce apoptosis of HCC cells in a dosedependent manner. Further western blotting assay showed that the inhibitory effects of EH-42 on cell growth and survival were caused by activating caspase 3/9, suppressing the phospho-STAT3 (Tyr 705) and downregulating anti-apoptotic proteins like Bcl-2/Bcl-xL. Moreover, migration and invasion abilities of HCC cells were also inhibited by EH-42 in the wound healing assay and transwell invasion assay. The potential mechanism was that EH-42 could inhibit HCC metastasis via reversing epithelial-mesenchymal transition and downregulating the secretion of MMPs.

Conclusion: Taken together, these findings suggested that EH-42 could be a potential therapeutic agent for HCC treatment.

Keywords: STAT3, apoptosis, migration, invasion, hepatocellular carcinoma.

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Article Details

VOLUME: 19
ISSUE: 7
Year: 2019
Page: [583 - 593]
Pages: 11
DOI: 10.2174/1568009619666181226094814
Price: $58

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