Introduction Hepatocellular carcinoma (HCC) is the 5th most common malignancy worldwide and the 3rd leading cause of cancer-related death. Currently, sorafenib is the only drug that has been approved by the U.S. FDA for patients with advanced HCC. However, its improvement on patient outcomes is modest, and the median survival time is only prolonged 2~3 months. Therefore, more effective novel agents are urgently needed for HCC therapy.
Method A novel benzimidazole derivative bearing pyrolidine side chain was synthesised. The HuH7 xenograft model was used to examine the antitumor activity in-vivo. Adverse effects (body weight, serum parameters, liver function and pathology) of mice were evaluated. Intratumoral signalling pathways were assessed by Western blot, Q-PCR and IHC staining.
Results Administration of this novel benzimidazole derivative bearing pyrolidine side chain compound significantly decreased HCC markers ć α-fetoprotein, glypican-3 and survivin expression and suppressed tumour growth. The phosphorylations of Akt and JNK in HuH7 xenograft tumour were also decreased. Meanwhile, there were no adverse effects in the liver and kidney of mice treated with this compound.
Conclusion Administration of the novel benzimidazole derivative bearing a pyrolidine side chain compound exerted significant antitumor activity in preclinical HCC models, which potentially suggests its use as a novel therapeutic strategy for patients with HCC.
Disclosure of Interest None Declared
- Benzimidazole derivative
- Hepatocellular carcinoma
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