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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
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Elevated extracellular calcium ions accelerate the proliferation and migration of HepG2 cells and decrease cisplatin
Haozhe Xu1, Yiming Zhou1, Jing Guo2
1Department of Geriatrics, Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Journal of Biomedical Research
|September 26, 2023
Summary
Extracellular calcium ions promote hepatoblastoma cell growth and migration by activating focal adhesion kinase (FAK) and Ca2+/calmodulin-dependent kinase II (CaMKII). These calcium-mediated pathways also increase resistance to cisplatin and impact immune cell infiltration in tumors.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Hepatoblastoma is the most common pediatric liver cancer.
- HepG2 cells, derived from hepatoblastoma, typically form cell clumps in culture.
- Extracellular calcium ions are implicated in various cellular processes, including tumorigenesis.
Purpose of the Study:
- To investigate the role of extracellular calcium ions in HepG2 cell behavior and hepatoblastoma progression.
- To elucidate the molecular mechanisms by which calcium influences cell proliferation, migration, and drug resistance.
- To explore the correlation between FAK and CaMKII expression and the tumor immune microenvironment in hepatoblastoma.
Main Methods:
- Treatment of HepG2 cells with extracellular calcium ions and specific inhibitors (FAK, CaMKII).
- Assessment of cell morphology, proliferation, migration, epithelial-mesenchymal transition (EMT) markers, and cisplatin sensitivity.
- Analysis of FAK and CaMKII expression levels in hepatoblastoma tissues and their correlation with immune cell infiltration (ImmunoScore, CD8+ T cells, NK cells) and immune checkpoint molecules (PDCD1, LAG3, TNFSF9, TNFRSF4, TNFRSF18).
Main Results:
- Extracellular calcium induced morphological changes, enhanced EMT, and promoted HepG2 cell proliferation and migration.
- Calcium ions upregulated the phosphorylation of focal adhesion kinase (FAK), protein kinase B, and p38 MAPK.
- Inhibitors of FAK or Ca2+/calmodulin-dependent kinase II (CaMKII) reversed calcium-induced effects. Calcium decreased cisplatin sensitivity and increased FAK and CaMKII expression in hepatoblastoma, correlating with reduced immune cell infiltration and altered immune marker expression.
Conclusions:
- Extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMKII, enhancing cisplatin resistance.
- FAK and CaMKII influence immune cell infiltration and responses within the tumor microenvironment.
- FAK and CaMKII represent potential therapeutic targets for hepatoblastoma treatment.
