Fig. 6

Schematic diagram depicting the synergistic effects of lovastatin with lapatinib. Through inhibiting HMGCR activity, lovastatin reduces cellular cholesterol contents and hence alters the physical properties of the cell membrane, conferring increased fluidity but decreased rigidity. These changes facilitates the internalization of cell surface ErbB2, which leads to its intracellular degradation through endosome to lysosome sorting. Reduced cellular ErbB2 expression sensitizes ErbB2-positive breast cancer cells to ErbB2 kinase inhibitors exemplified by lapatinib and neratinib, which collectively elicit more potent anti-cancer effects