Columbamine-Mediated PTEN/AKT Signal Pathway Regulates the Progression of Glioma
Hai-Tao Niu1, Yang Liu1, Yan-Zhou Wang1
1Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, People's Republic of China.
Purpose:
At present, comprehensive therapy has been widely used in the treatment of glioma, but the curative effect is not good, and the survival rate of patients is low. Therefore, it is crucial to explore further the regulatory mechanism of the occurrence and development of glioma and find potential therapeutic targets. We aimed to investigate the columbamine (a tetrahydroisoquinoline alkaloid derived from the rhizome of Chinese herbal medicine Rhizoma Coptidis) on glioma progression.
Methods:
MTT, clone formation assay, wound healing assay, and transwell assay were performed to detect the cell viability, proliferation, migration, and invasion ability. Flow cytometry, TUNEL, and Western blot were used to identify the apoptosis level in glioma cells. PTEN inhibitor (SF1670) and AKT activator (SC79) were used to explore the mechanism of columbamine on glioma cell progression.
Results:
Columbamine inhibits proliferation, migration, invasion, and induces apoptosis in glioma cell lines (SHG44 and U251). Columbamine prevents phosphorylation of AKT and promotes the expression of PTEN. Blocking PTEN level or inducing phosphorylation of AKT attenuates columbamine function on SHG44 cells proliferation, metastasis, and apoptosis.
Conclusion:
In this research, we find that columbamine could inhibit proliferation and metastasis of glioma cell lines, and promote apoptosis of glioma cell lines via regulating PTEN/AKT signal pathway. It provides a new theoretical basis for the development of anti-glioma drugs.
Insights
Columbamine, a natural compound, inhibits glioma cell growth, migration, and invasion while promoting apoptosis. It functions by regulating the PTEN/AKT pathway, offering potential for new anti-glioma drug development.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Glioma treatment remains challenging with low survival rates.
- Understanding glioma progression mechanisms is crucial for identifying therapeutic targets.
- Columbamine, derived from Rhizoma Coptidis, is investigated for its anti-glioma potential.
Purpose of the Study:
- To investigate the effect of columbamine on glioma progression.
- To elucidate the mechanism of columbamine action in glioma cells.
- To explore columbamine as a potential therapeutic agent for glioma.
Main Methods:
- Cell viability, proliferation, migration, and invasion assays (MTT, clone formation, wound healing, Transwell).
- Apoptosis assessment via flow cytometry and TUNEL assays.
- Western blot analysis to evaluate PTEN and AKT pathway modulation, using PTEN inhibitor (SF1670) and AKT activator (SC79).
Main Results:
- Columbamine significantly inhibited proliferation, migration, and invasion in glioma cell lines (SHG44, U251).
- Columbamine induced apoptosis in glioma cells.
- Columbamine treatment prevented AKT phosphorylation and increased PTEN expression, suggesting PTEN/AKT pathway regulation.
Conclusions:
- Columbamine demonstrates potent anti-glioma effects by inhibiting proliferation and metastasis while inducing apoptosis.
- The mechanism involves the regulation of the PTEN/AKT signaling pathway.
- Columbamine presents a promising new therapeutic strategy for glioma treatment.
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