Targeting LRH‑1 in hepatoblastoma cell lines causes decreased proliferation

Area of Science:

• Pediatric oncology
• Molecular biology
• Hepatobiliary diseases

Background:

• Hepatoblastoma is a common childhood liver cancer, often unresectable and drug-resistant.
• Advanced hepatoblastoma treatment remains a significant clinical challenge.
• The role of liver receptor homolog‑1 (LRH‑1) in hepatoblastoma is currently unknown.

Purpose of the Study:

• To investigate the role of LRH‑1 in hepatoblastoma progression.
• To evaluate the therapeutic potential of LRH‑1 antagonists (LRAs) in hepatoblastoma.

Main Methods:

• Analysis of LRH‑1 mRNA and protein expression in human hepatoblastoma cell lines.
• LRH‑1 knockdown experiments to assess effects on cell proliferation and gene expression.
• Treatment of hepatoblastoma cells with an LRH‑1 antagonist (LRA) and doxorubicin.

Main Results:

• LRH‑1 expression was significantly higher in aggressive hepatoblastoma cell lines (HepG2, HuH6) compared to less aggressive ones (HepT1) and normal liver cells (THLE‑2).
• LRH‑1 knockdown reduced hepatoblastoma cell proliferation by downregulating cyclin D1 (CCND1) and c‑Myc.
• LRA treatment inhibited cell proliferation and colony formation, induced G1 cell cycle arrest via CCND1 inhibition, and potentiated doxorubicin's cytotoxicity.

Conclusions:

• LRH‑1 plays a critical role in hepatoblastoma progression.
• LRH‑1 antagonists represent a promising novel therapeutic strategy for treating hepatoblastoma, potentially in combination with chemotherapy.