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Pyrazolamide derivative T1 inhibits hepatocellular carcinoma cell proliferation through MAPK pathway modulation

Yuting Zhang1, Yao Chen2, Huina Lv1

  • 1Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, PR China; Department of Oncology, Anhui Medical University, Hefei, Anhui 230032, PR China.

International Immunopharmacology
|June 7, 2025
PubMed

Insights

A novel compound, T1, shows significant potential as a liver cancer treatment. This pyrazole amide derivative effectively inhibits cancer cell growth and induces apoptosis, offering a promising new therapeutic option for hepatocellular carcinoma.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide.
  • Development of novel, effective chemotherapeutic agents for HCC is crucial.

Purpose of the Study:

  • To design, synthesize, and evaluate a novel pyrazole amide derivative, T1, for its therapeutic potential against liver cancer.
  • To investigate the in vitro and in vivo anti-cancer effects of T1 on hepatocellular carcinoma cells.

Main Methods:

  • In vitro assays: CCK-8, colony formation, transwell migration, immunofluorescence, and western blotting.
  • In vivo studies: HuH-7 xenograft mouse model.
  • Molecular analyses: Transcriptome sequencing and western blotting to elucidate mechanism of action.

Main Results:

  • T1 exhibited significant anti-proliferative and anti-migratory effects on HuH-7 and HepG2 cells, with an IC50 of 47.7 μg/mL in HuH7 cells.
  • T1 induced apoptosis and modulated the MAPK signaling pathway, affecting apoptosis-related protein expression.
  • In vivo studies demonstrated T1's efficacy in inhibiting tumor growth in a xenograft mouse model, comparable to sorafenib.

Conclusions:

  • The novel pyrazole amide derivative T1 demonstrates potent anti-cancer activity against hepatocellular carcinoma.
  • T1's mechanism involves modulation of the MAPK pathway and induction of apoptosis.
  • T1 represents a promising candidate for further development as a chemotherapeutic agent for HCC treatment.
Keywords:
ApoptosisCellular mechanismsHepatocellular carcinomaMAPK pathwaycancer therapy

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