PHA-E is a
natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in
lung cancer cells. Because
EGF is the major in vivo competitor to
PHA-E in clinical application,
PHA-E must be proved that has better affinity to EGFR than
EGF. This study would focus on how
PHA-E tightly bind to EGFR and the results would compare with
EGF. The adhesion force, measured by AFM, between EGFR and
PHA-E was 207.14±74.42 pN that was higher than
EGF (183.65±86.93 pN). The equilibrium dissociation constant of
PHA-E and
EGF to EGFR was 2.4 10(-9)±1.4 10(-9) and 7.3 10(-8)±2.7 10(-8), respectively, that could evaluate binding affinity. The result showed that binding affinity of
PHA-E to EGFR was one order higher than
EGF to EGFR. In the results of flow cytometer and confocal microscope, we found binding efficiency of
EGF to EGFR was decrease as the concentration of
PHA-E increased. In the analysis of Western blot, treatment of A-549 cells with
PHA-E resulted in a dose-dependent decrease in EGFR phosphorylation. In conclusion, we found that
PHA-E had better adhesion force and binding affinity to EGFR than that of the
EGF. The interaction between
PHA-E and EGFR could block
EGF binding and then inhibit EGFR phosphorylation.
PHA-E could be developed into a new target molecule for
lung cancer treatment that could be immobilized on the
drug carrier to guide therapeutic particles to the
tumor site.