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EH-42, a novel small molecule induces apoptosis and inhibits migration and invasion of human hepatoma cells through suppressing STAT3 signaling pathway

[ Vol. 19 , Issue. ]

Author(s):

Qi-Zhe Gong , Di Xiao , Gui-Yi Gong, Jian Xu , Xiao-Dong Wen*, Feng Feng* and Wei Qu *Pages 1-1 (1)

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 double-staining assay, EH-42 could suppress the growth and induce apoptosis of HCC cells in a dose-dependent 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.

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

Keywords:

STAT3, apoptosis, migration, invasion, hepatocellular carcinoma

Affiliation:

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009



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