Lapatinib Promotes Apoptosis in Hepatoma Cells by Regulating SPP1 Expression

Introduction: Lapatinib, a novel targeted anti-tumor drug in clinical use, demonstrates notable potential for liver cancer treatment. However, its mechanism of action in liver hepatocellular carcinoma (LIHC) remains poorly understood. This investigation sought to clarify the function of secreted phosphoprotein 1 (SPP1) in LIHC and investigate the anti-tumor effects of lapatinib on SPP1 expression.

Methods: We analyzed data from normal liver and LIHC specimens obtained from The Cancer Genome Atlas (TCGA) and the GSE6764 dataset using R version 4.2.1. SPP1 protein expression in LIHC patients and its impact on patient prognosis were evaluated. Western blotting evaluated lapatinib-induced alterations in SPP1 protein levels in hepatoma cells. Cell Counting Kit-8 (CCK-8) assays measured lapatinib's impact on hepatoma cell growth and proliferation.

Results and Discussion: SPP1 level was notably elevated in LIHC specimens versus normal liver tissues (P < 0.01). The survival outcomes were notably inferior in cases displaying elevated SPP1 levels versus those with reduced levels (P < 0.05). CCK-8 analyses demonstrated that a decrease in SPP1 expression leads to a significant inhibition of growth and proliferation in the LIHC cell line HepG2, while lapatinib can inhibit the survival of liver cancer cells. Western blotting analyses revealed that lapatinib treatment reduced SPP1 expression in HepG2 cells, increased the ratio of BAX/Bcl2, and triggered apoptosis in cells.

Conclusion: These observations demonstrate that the expression of SPP1 is associated with disease progression and survival in patients with LIHC. Lapatinib exerts its anti-tumor effects in LIHC by downregulating SPP1 expression and promoting apoptosis in hepatoma cells.