PIM447 inhibits oncogenesis and potentiates cisplatin effects in hepatoblastoma
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In brief
In brief
PIM447, a novel PIM kinase inhibitor, demonstrates significant anti-tumor activity in hepatoblastoma by reducing cell viability, proliferation, motility, and cancer stem cell markers while increasing apoptosis. When combined with cisplatin, PIM447 shows enhanced therapeutic efficacy, suggesting potential as a combination therapy for this pediatric liver cancer.
Written by the GCMD Library team from the article.
Abstract
Background
: Novel therapies are needed for patients with hepatoblastoma because of an increasing incidence of disease and poor prognosis for advanced, refractory, and recurrent disease. PIM kinases promote tumorigenesis in hepatoblastoma. A novel PIM inhibitor, PIM447, has shown promise in inhibiting oncogenesis in hematologic and lymphoid malignancies. We hypothesized that PIM inhibition with PIM447 would result in decreased tumorigenesis in hepatoblastoma.
Methods
: The effects of PIM447 on hepatoblastoma viability, proliferation, motility, apoptosis, and tumor cell stemness were assessed in HuH6, a human hepatoblastoma cell line, and COA67, a human hepatoblastoma patient-derived xenograft.
Results
: PIM447 significantly decreased the viability, proliferation, and motility of HuH6 and COA67 cells. Apoptosis significantly increased following PIM447 treatment. PIM447 had a significant impact on tumor cell stemness as evidenced by decreased expression of CD133 and reduced ability of HuH6 and COA67 cells to form tumorspheres. Furthermore, combining PIM447 with cisplatin resulted in a significant decrease in cell viability compared to either treatment alone.
Conclusion
: We showed that PIM447 inhibits oncogenesis and potentiates the effects of cisplatin in hepatoblastoma and, therefore, warrants further investigation as a potential therapeutic agent for hepatoblastoma.