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Inhibition of Colorectal Cancer Cell Progression by Picroside II Through Modulation of the Notch1 Signaling Pathway
Rui Wang1,2, Wei Zhang3, Fang Wang3
1Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract:
This study aimed to investigate the biological effects of Picroside II on colorectal cancer (CRC) cells, including its impacts on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), and to explore whether its mechanism of action involves modulation of the Notch1 signaling pathway. Human CRC cell lines SW480 and SW620 were treated with various concentrations of Picroside II (10-100 μM). Cell proliferation was assessed using the CCK-8 assay, colony formation assay, and EdU incorporation assay. Migration and invasion capacities were evaluated by wound healing and Transwell assays. The expression levels of EMT-related markers (E-cadherin, N-cadherin, Vimentin, ZEB2) and key proteins in the Notch1 pathway (Notch1, Cleaved Notch1, RBP, HES1) were analyzed by Western blotting. Statistical analysis was performed using one-way ANOVA and Student's t-test. Picroside II inhibited the proliferation of SW480 and SW620 cells in a dose- and time-dependent manner, reduced colony formation ability, and decreased DNA synthesis activity. Treatment with Picroside II suppressed the migratory and invasive abilities of CRC cells, accompanied by upregulation of E-cadherin and downregulation of N-cadherin, Vimentin, and ZEB2. Furthermore, Picroside II exposure led to a decrease in the expression of Notch1, Cleaved Notch1, RBP, and HES1 proteins in a concentration-dependent manner. Picroside II suppresses CRC cell progression in vitro by inhibiting the Notch1 signaling pathway, providing a preliminary molecular basis for further in vivo investigation.
Insights
Picroside II effectively inhibits colorectal cancer (CRC) cell progression by suppressing proliferation, migration, and invasion. This compound acts by downregulating the Notch1 signaling pathway, offering a potential therapeutic strategy for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colorectal cancer (CRC) remains a significant global health challenge.
- Identifying novel therapeutic agents targeting cancer cell progression is crucial.
- The Notch1 signaling pathway is implicated in various cancers, including CRC.
Purpose of the Study:
- To investigate the anti-cancer effects of Picroside II on colorectal cancer (CRC) cells.
- To determine the impact of Picroside II on CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- To explore the role of the Notch1 signaling pathway in mediating the effects of Picroside II.
Main Methods:
- Human CRC cell lines (SW480, SW620) were treated with varying concentrations of Picroside II.
- Cell proliferation was assessed using CCK-8, colony formation, and EdU assays.
- Migration, invasion, EMT markers, and Notch1 pathway proteins were analyzed via wound healing, Transwell, and Western blotting assays.
Main Results:
- Picroside II significantly inhibited CRC cell proliferation, colony formation, and DNA synthesis.
- Treatment with Picroside II reduced CRC cell migration and invasion, altering EMT markers (upregulating E-cadherin, downregulating N-cadherin, Vimentin, ZEB2).
- Picroside II decreased the expression of Notch1, Cleaved Notch1, RBP, and HES1 proteins in a dose-dependent manner.
Conclusions:
- Picroside II exhibits potent anti-cancer properties against colorectal cancer cells in vitro.
- The mechanism involves the inhibition of the Notch1 signaling pathway.
- Picroside II represents a promising candidate for further investigation as a CRC therapeutic agent.
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