首页|Elevated extracellular calcium ions accelerate the proliferation and migration of HepG2 cells and decrease cisplatin sensitivity

Elevated extracellular calcium ions accelerate the proliferation and migration of HepG2 cells and decrease cisplatin sensitivity

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Hepatoblastoma is the most frequent liver malignancy in children.HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture.Intriguingly,we observed that the addition of calcium ions reduced cell clumping and disassociated HepG2 cells.The calcium signal is in connection with a series of processes critical in the tumorigenesis.Here,we demonstrated that extracellular calcium ions induced morphological changes and enhanced the epithelial-mesenchymal transition in HepG2 cells.Mechanistically,calcium ions promoted HepG2 proliferation and migration by up-regulating the phosphorylation levels of focal adhesion kinase(FAK),protein kinase B,and p38 mitogen-activated protein kinase.The inhibitor of FAK or Ca2+/calmodulin-dependent kinase Ⅱ(CaMK Ⅱ)reversed the Ca2+-induced effects on HepG2 cells,including cell proliferation and migration,epithelial-mesenchymal transition protein expression levels,and phosphorylation levels of FAK and protein kinase B.Moreover,calcium ions decreased HepG2 cells'sensitivity to cisplatin.Furthermore,we found that the expression levels of FAK and CaMK Ⅱ were increased in hepatoblastoma.The group with high expression levels of FAK and CaMK Ⅱ exhibited significantly lower ImmunoScore as well as CD8+T and NK cells.The expression of CaMK Ⅱ was positively correlated with that of PDCD1 and LAG3.Correspondingly,the expression of FAK was negatively correlated with that of TNFSF9,TNFRSF4,and TNFRSF18.Collectively,extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMK Ⅱ and enhances cisplatin resistance.FAK and CaMK Ⅱ shape immune cell infiltration and responses in tumor microenvironments,thereby serving as potential targets for hepatoblastoma.

HepG2hepatoblastomacalcium ionFAKCaMK Ⅱcisplatin resistance

Haozhe Xu、Yiming Zhou、Jing Guo、Tao Ling、Yujie Xu、Ting Zhao、Chuanxin Shi、Zhongping Su、Qiang You

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Department of Geriatrics,Medical Center for Digestive Diseases,the Second Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210011,China

Affiliated Cancer Hospital & Institute,Guangzhou Medical University,Guangzhou,Guangdong 510095,China

Department of Medical Oncology,Fudan University Shanghai Cancer Center,Shanghai 200032,China

Division of General Surgery,the Second Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210011,China

Department of Geriatric Gastroenterology,the First Affiliated Hospital of Nanjing Medical University,Institute of Neuroendocrine Tumor,Nanjing Medical University,Nanjing,Jiangsu 210029,China

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Jiangsu Medical Scientific Research Project of Jiangsu Health Commission789 Outstanding Talent Program of SAHNMUGuangzhou Key Medical Discipline Construction ProjectNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

789ZYRC 2020701028187040981671543

2023

10.7555/JBR.37.20230067

生物医学研究杂志(英文版)
南京医科大学

生物医学研究杂志(英文版)

CSCD
影响因子：0.794
ISSN：1674-8301
年,卷(期)：2023.37(5)
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