title: 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.
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jong-Rung
authors.initials: JR
authors.lastname: Tsai
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Po-Len
authors.initials: PL
authors.lastname: Liu
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Division of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shah-Hwa
authors.initials: SH
authors.lastname: Chou
authors.affiliation: Department of Surgery, Yuan's General Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Chan
authors.initials: MC
authors.lastname: Yang
authors.affiliation: Department of Health Management, Division of Thoracic Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jhi-Jhu
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Cheng-Hsin General Hospital, Faculty of Medicine, and Cardiovascular Research Centre, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Hsian
authors.initials: WH
authors.lastname: Yin
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Inn-Wen
authors.initials: IW
authors.lastname: Chong
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020441:Ginkgo biloba / Q000737:chemistry*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000096983:Ginkgo Extract
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D055551:HSP27 Heat-Shock Proteins; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract