Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Hepatocellular carcinoma (HCC) exhibits resistance to paclitaxel, a common chemotherapeutic agent.
• The underlying mechanisms of paclitaxel resistance in HCC, particularly involving alpha fetoprotein (AFP), require further investigation.

Purpose of the Study:

• To investigate the role of alpha fetoprotein (AFP) in mediating paclitaxel resistance in hepatocellular carcinoma (HCC) cells.
• To explore the potential of targeting AFP as a therapeutic strategy to overcome paclitaxel resistance in HCC.

Main Methods:

• Cell viability assays were performed on HCC cell lines (HLE, Bel 7402, L-02) treated with paclitaxel.
• Gene transfection with pcDNA3.1-AFP vectors and AFP-siRNA was employed to modulate AFP expression.
• Expression levels of apoptosis-related proteins (caspase-3, Ras, Survivin) and stemness markers (CD44, CD133) were analyzed.

Main Results:

• Paclitaxel inhibited HCC cell viability in a dose- and time-dependent manner.
• Overexpression of AFP via pcDNA3.1-AFP vectors conferred resistance to paclitaxel in HLE and L-02 cells.
• Silencing AFP with AFP-siRNA increased Bel 7402 cell sensitivity to paclitaxel.
• Paclitaxel-induced apoptosis and inhibition of Ras and Survivin were counteracted by AFP overexpression.
• AFP overexpression also prevented paclitaxel-induced caspase-3 cleavage.
• Bel 7402 cell resistance was linked to CD44 and CD133 expression.

Conclusions:

• Alpha fetoprotein (AFP) plays a crucial role in promoting paclitaxel resistance in HCC cells.
• AFP antagonizes paclitaxel-induced apoptosis by inhibiting caspase-3 activity and promoting Ras and Survivin expression.
• Targeted inhibition of AFP, in combination with paclitaxel, presents a promising therapeutic strategy for overcoming paclitaxel resistance in HCC patients.