Polo‐like kinase 1 inhibition suppresses hepatitis B virus X protein‐induced transformation in an in vitro model of liver cancer progression†

Abstract

Partial polyploidy induced by pX is not immediately associated with oncogenic transformation. Continued DNA damage for 40 cell generations is reproducibly associated with loss of p53 function, enhanced expression of Plk1, and oncogenic transformation. Because Plk1 expression is also elevated in HBV-HCC tumors, this in vitro cellular model simulates liver cancer progression and pathogenesis in chronic HBV patients. Inhibition of Plk1 activity suppresses pX-mediated oncogenic transformation, identifying Plk1 as a promising therapeutic target for HBV-mediated HCC.