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Triptonide inhibits growth and metastasis in HCC by suppressing EGFR/PI3K/AKT signaling
Hao Zhang1, Yingxuan Mao2, Xiaomeng Zou2
1Department of Medical Imaging, Heilongjiang Provincial Hospital, Harbin, China.
Abstract:
Liver cancer represents one of the deadliest cancers, with a rising incidence worldwide. Triptonide is found in the traditional Chinese medicinal plant Tripterygium wilfordii Hook. This study aimed to examine the anticancer properties of triptonide in human hepatocellular carcinoma (HCC). HCC cells were administered with triptonide at various levels, and CCK-8 and colony formation assays were carried out for detecting HCC cell proliferation. Then, cell apoptosis and cell cycle distribution were evaluated by flow cytometry. Tumor growth was monitored noninvasively by ultrasound imaging. Cell migration and invasion were quantitated by wound healing and Transwell assays. A metastasis model was established via tail vein injection of HCC cells in nude mice. Immunoblot was performed to quantitate the expression of proteins involved in the EGFR/PI3K/AKT signaling and its downstream effectors. Triptonide repressed cell proliferation and induced cell cycle arrest and apoptosis in cultured HCC cells, and suppressed tumor growth in vivo. In addition, triptonide inhibited EMT, migration and invasion in cultured HCC cells, and lung metastasis in nude mice. Mechanistically, triptonide acted by inhibiting the EGFR/PI3K/AKT signaling and regulated its downstream effectors, e.g., the cell cycle-associated protein cyclin D1, the apoptosis-related protein Bcl-2, the EMT marker E-cadherin, and the invasion-related protein MMP-9. Triptonide suppresses proliferation, EMT, migration and invasion, and promotes apoptosis and cell cycle arrest by repressing the EGFR/PI3K/AKT signaling. Therefore, triptonide might be considered for liver cancer treatment.
Insights
Triptonide, derived from Tripterygium wilfordii, effectively combats liver cancer by inhibiting hepatocellular carcinoma (HCC) cell proliferation and metastasis. This natural compound promotes apoptosis and cell cycle arrest, offering a potential new avenue for liver cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Traditional Chinese Medicine
Background:
- Liver cancer, specifically hepatocellular carcinoma (HCC), presents a significant global health challenge with increasing incidence.
- Tripterygium wilfordii Hook. is a traditional Chinese medicinal plant containing the compound triptonide.
- Exploring novel therapeutic agents for liver cancer is crucial.
Purpose of the Study:
- To investigate the anticancer properties of triptonide against human hepatocellular carcinoma (HCC).
- To elucidate the molecular mechanisms underlying triptonide's effects on HCC cells and tumor growth.
Main Methods:
- In vitro assays (CCK-8, colony formation, flow cytometry, wound healing, Transwell) were used to assess HCC cell proliferation, apoptosis, cell cycle, migration, and invasion.
- In vivo studies involved noninvasive ultrasound imaging of tumor growth and a metastasis model in nude mice.
- Western blotting was employed to analyze the expression of proteins in the EGFR/PI3K/AKT signaling pathway and its downstream targets.
Main Results:
- Triptonide significantly repressed HCC cell proliferation, induced apoptosis, and caused cell cycle arrest in vitro.
- In vivo, triptonide suppressed tumor growth and inhibited epithelial-mesenchymal transition (EMT), migration, invasion, and lung metastasis.
- Triptonide functions by inhibiting the EGFR/PI3K/AKT signaling pathway, affecting key proteins like cyclin D1, Bcl-2, E-cadherin, and MMP-9.
Conclusions:
- Triptonide exhibits potent anticancer effects against hepatocellular carcinoma by inhibiting proliferation, EMT, migration, and invasion, while promoting apoptosis and cell cycle arrest.
- The mechanism involves the repression of the EGFR/PI3K/AKT signaling pathway.
- Triptonide demonstrates significant therapeutic potential for liver cancer treatment.
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