Regorafenib delays the proliferation of hepatocellular carcinoma by inducing autophagy

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern with limited treatment options.
• Autophagy plays a complex role in cancer, potentially promoting or inhibiting tumor progression.
• Understanding the mechanisms by which drugs affect cancer cell autophagy is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the effects of regorafenib on hepatocellular carcinoma (HCC) autophagy.
• To determine if regorafenib-induced cell death in HCC is dependent on autophagy.
• To explore the potential of regorafenib as an adjunctive therapy for HCC.

Main Methods:

• HepG2 and Hep3B cells were treated with regorafenib.
• Autophagy was assessed using GFP-LC3 transfection.
• Akt/mTOR signaling pathway activation was analyzed via western blot.
• Cell viability was measured using MTT assays.
• The role of autophagy in cell death was studied using autophagy inhibitors 3-MA and CQ.

Main Results:

• Regorafenib (20 μM) significantly induced autophagy in liver cancer cells.
• Regorafenib-induced cell death was partially dependent on autophagy, as shown by 3-MA and CQ treatments.
• Regorafenib inhibited the activation of the Akt/mTOR signaling pathway.
• Combination therapy with regorafenib and CDDP demonstrated a stronger growth inhibitory effect on HCC cells.

Conclusions:

• Regorafenib effectively induces autophagy and contributes to cell death in hepatocellular carcinoma.
• The Akt/mTOR pathway is implicated in regorafenib's effects on HCC autophagy.
• Regorafenib shows promise as an adjunctive therapy for HCC, potentially overcoming apoptosis resistance by modulating autophagy.