ArticleAmerican journal of cancer research2025
Synergistic therapeutic effects of pertuzumab and pyrrolitinib in HER-2-positive breast cancer: modulation of the PI3K/AKT pathway.
Article in American journal of cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo investigate the underlying mechanism of pertuzumab combined with pyrrolitinib in the treatment of breast cancer.
methodsReal-time PCR and Western blot (WB) were used to detect the expression of HER-2 in breast cancer cells (MCF-10A, BT-474 and SK-BR-3). Subsequently, BT-474 cells were treated with different concentrations of pertuzumab (0, 0.1, 0.5, 1, 5, 10 μg/mL), pyrrolizinib (0, 2, 4, 6, 8, 10 nMol/L) or a synergistic mixture of pertuzumab and pyrrolizinib. The cell viability, migration, invasion and programmed cell death were detected by CCK-8, cell colony formation, wound healing, transwell migration, TUNEL apoptosis assay and WB. KEGG pathway analysis was used to identify key pathways with HER-2 involvement. String database was used to analyze the relationship between HER-2 and PI3K/AKT signaling pathway related proteins. Subsequently, the effects of HER-2 knockdown on PI3K/AKT signaling pathway and cell function were investigated.
resultsElevated HER-2 expression was observed in breast cancer tissues and cells. The combination of pertuzumab and pyrrolitinib effectively reduced HER-2 levels, inhibited cell viability, proliferation, migration and infiltration, and promoted apoptosis. Knockdown of HER-2 inhibited the viability, proliferation, migration and invasion, downregulated the expression of PI3K and AKT, and increased the apoptosis of BT-474 cells, with these effects restored by IGF-1.
conclusionPertuzumab and pyrrolizinib target HER-2 to downregulate the PI3K/AKT signaling pathway, thereby inhibiting breast cancer cells.
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