Ginkgo biloba extract decreases non-small cell lung cancer cell migration by downregulating metastasis-associated factor heat-shock protein 27.

Abstract

Heat-shock proteins (HSPs) are molecular chaperones that protect proteins from damage. HSP27 expression is associated with cancer transformation and invasion. Ginkgo biloba extract (EGb761), the most widely sold herbal supplement, has antiangiogenic effects and induces tumor apoptosis. Data regarding the effect of EGb761 on HSP expression is limited, particularly in cancer. HSP27 expression in paired tumors and normal lung tissues of 64 patients with non-small cell lung cancer (NSCLC) were detected by real-time PCR, western blotting, and immunohistochemistry. NSCLC cell lines (A549/H441) were used to examine the migratory abilities in vitro. NSCLC tissue showed higher HSP27 expression than normal lung tissue. Kaplan-Meier survival analysis showed that NSCLC patients with low HSP27 expression ratio (<1) had significantly longer survival time than those with a high expression ratio (>1) (p = 0.04). EGb761 inhibited HSP27 expression and migratory ability of A549/H441 cells, which is the same as HSP27-siRNA transfection effect. Moreover, EGb761 treatment activated the AKT and p38 pathways and did not affect the expression of PI3K, ERK, and JNK pathways. HSP27 is a poor prognostic indicator of NSCLC. EGb761 can decrease the migration ability of A549/H441 by inhibiting HSP27 expression most likely through AKT and p38 MAPK pathways activation.