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Lapatinib Promotes Apoptosis in Hepatoma Cells by Regulating SPP1 Expression
Dang Wang1,2, Keyi Jiang1,2, Hongqi Feng3,2
1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China.
Secreted phosphoprotein 1 (SPP1) is elevated in liver hepatocellular carcinoma (LIHC) and linked to poor prognosis. The targeted drug lapatinib inhibits LIHC cell growth by reducing SPP1 expression and promoting apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Liver hepatocellular carcinoma (LIHC) is a significant global health concern.
- The precise mechanisms of targeted therapies like lapatinib in LIHC require further elucidation.
- Secreted phosphoprotein 1 (SPP1) is implicated in various cancers, but its role in LIHC is not fully understood.
Purpose of the Study:
- To investigate the role of SPP1 in LIHC progression and patient prognosis.
- To explore the anti-tumor effects of lapatinib on SPP1 expression in LIHC.
- To elucidate the molecular mechanisms by which lapatinib exerts its effects in LIHC.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) and GSE6764 datasets for SPP1 expression in LIHC.
- Evaluation of SPP1 expression and its correlation with patient survival outcomes.
- In vitro studies using HepG2 cells to assess lapatinib's effects on SPP1 levels, cell proliferation (CCK-8 assay), and apoptosis (Western blotting for BAX/Bcl2 ratio).
Main Results:
- SPP1 expression was significantly higher in LIHC tissues compared to normal liver tissues (P < 0.01).
- Elevated SPP1 levels correlated with inferior patient survival outcomes in LIHC (P < 0.05).
- Lapatinib treatment reduced SPP1 expression, inhibited HepG2 cell proliferation, increased the BAX/Bcl2 ratio, and induced apoptosis.
Conclusions:
- SPP1 is a potential biomarker for disease progression and survival in LIHC patients.
- Lapatinib demonstrates anti-tumor activity in LIHC by downregulating SPP1 expression.
- Lapatinib promotes apoptosis in hepatoma cells, contributing to its therapeutic effect in LIHC.
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