Phosphatidylinositol-3-kinase/Protein Kinase B Signaling Pathway: A Pivotal Factor for Stimulating Multidrug Resistance in Hepatocellular Carcinoma Cells

Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor. Chemotherapy is one of its principal modes of treatment, but multidrug resistance (MDR) poses an obstacle in HCC treatment. MDR is mainly mediated through drug transmembrane transporter activity, apoptosis inhibitory pathway abnormality, and changes in the intracellular enzyme. On top of that, phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway dysregulation is also one of the most common mechanisms of MDR. This signaling pathway plays critical roles in the differentiation, proliferation, and apoptosis of cancer cells, and is a new target of MDR treatment. This review article discusses the mechanisms of MDR in HCC with a strong emphasis on the significance and role of PI3K/Akt pathway in MDR, and the reversal of MDR by inhibiting PI3K/Akt pathway.