Introduction
Hepatocellular carcinoma (HCC) is a common malignancy in humans. In 2016, one million new cases of HCC and 829,000 cancer deaths were reported worldwide. In the US, the 5-year survival rate between 2006 and 2012 was approximately 18%. Diagnosis of HCC at an earlier stage can improve the 5-year survival rate of resectable HCC up to 50%; however, the survival rate of advanced, unresectable HCC remains low.
The HSD3B enzyme family, including HSD3B1 and HSD3B2, is a critical component of the androgen and estrogen metabolism pathway. A total of 44 out of 57 HCC tumor tissue (77.2%) showed increased HSD3B1 expression. The increased HSD3B1 in tumors was significantly associated with advanced HCC.
In vitro, the knockdown of HSD3B1 expression in Mahlavu HCC cells by a short hairpin RNA (shRNA) led to significant decreases in colony formation and cell migration. Trilostane-mediated inhibition of HSD3B1 in different HCC cells also caused significant inhibition of clonogenicity and cell migration. In subcutaneous HCC Mahlavu xenografts, trilostane (30 or 60 mg/kg, intraperitoneal injection) significantly inhibited tumor growth in a dose-dependent manner. Furthermore, the combination of trilostane and sorafenib significantly enhanced the inhibition of clonogenicity and xenograft growth. HSD3B1 blockade was found to suppress the phosphorylation of extracellular signal-regulated kinase (ERK).
Conclusion: Trilostane significantly inhibited the growth of HCC by inhibiting HSD3B1 function and augmenting the efficacy of sorafenib.
Features / strengths
1.The role of HSD3B1 in liver cancer has never been explored. Our data revealed that 77.2% of liver cancer patients had elevated HSD3B1 expression.
2.In animal studies, inhibiting HSD3B1 with the drug trilostane has shown promising results in controlling liver cancer without significant side effects.
3.Combining this with sorafenib, an existing targeted therapy for liver cancer, has shown enhanced therapeutic efficacy.
Specification in detail
Under development
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