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JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells
Li-Hua Liu1,2, Chong-Kai Fang1,3, Fu-Cheng Ge3
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Background:
Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present.
Methods:
We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments.
Results:
We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies.
Conclusion:
Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.
Insights
Jianpi Huayu Decoction (JPHYD) inhibits liver cancer growth by blocking epithelial-mesenchymal transition (EMT). This traditional Chinese medicine increases Smad7 and decreases miR-21-5p, offering a potential new therapeutic strategy for hepatocellular carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Traditional Chinese Medicine
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern.
- Jianpi Huayu Decoction (JPHYD) shows potential in inhibiting HCC growth, but its underlying mechanisms require elucidation.
Purpose of the Study:
- To investigate the anti-cancer effects and molecular mechanisms of JPHYD on hepatocellular carcinoma cells.
- To determine JPHYD's impact on epithelial-mesenchymal transition (EMT) in HCC.
Main Methods:
- In vitro assays (CCK8, EdU, wound-healing, Transwell) using HCC cell lines (HepG2, MHCC97H).
- Western blot and qRT-PCR to analyze protein and microRNA expression (E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, Zeb1, miR-21-5p).
- In vivo xenograft tumor models and imaging in animals.
Main Results:
- JPHYD significantly inhibited proliferation, migration, and invasion of HCC cells.
- JPHYD modulated EMT markers by increasing E-cadherin and Smad7, while decreasing N-cadherin, Snail, Vimentin, Smad3, and Zeb1.
- JPHYD reduced the expression of miR-21-5p, which was found to promote HCC cell migration.
Conclusions:
- JPHYD exerts anti-cancer effects by inhibiting EMT in hepatocellular carcinoma.
- The mechanism involves upregulating Smad7 and downregulating miR-21-5p.
- JPHYD represents a promising therapeutic approach for liver cancer by targeting EMT.
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