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

In this study, a novel pyrazole amide derivative designated T1, was designed and synthesized to explore its therapeutic potential for liver cancer. The compound was evaluated for its effects on liver cancer cell viability, proliferation, migration, invasion, and apoptosis both in vitro and in vivo. The in vitro evaluation was conducted using several experimental techniques, including the CCK-8 assay, colony formation assay, transwell migration assay, immunofluorescence, and western blotting. T1 demonstrated an IC50 of 47.7 μg/mL in HuH7 liver cancer cells, showing significantly improved efficacy compared to standard chemotherapeutics, including capecitabine and 5-fluorouracil, and comparable efficacy to sorafenib (IC50 of 55.6 μg/ml). Furthermore, T1 significantly inhibited the proliferation, migration, and invasion of HepG2 and HuH-7 cells, while also inducing apoptosis. Transcriptome sequencing and western blotting analyses revealed that T1 modulates the MAPK signaling pathway, leading to the altered expression of apoptosis-related proteins, which contributes to the observed anti-cancer effects. In vivo studies using a HuH-7 xenograft mouse model confirmed the efficacy of T1, with tumor growth inhibition similar to that of sorafenib. These findings suggest that T1 holds significant promise as a potential chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC).