Tsai Jong-Rung, Liu Po-Len, Chen Yung-Hsiang, Chou Shah-Hwa, Yang Ming-Chan, Cheng Yu-Jen, Hwang Jhi-Jhu, Yin Wei-Hsian, Chong Inn-Wen
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.
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
PLoS One. 2014 Mar 11;9(3):e91331. doi: 10.1371/journal.pone.0091331. eCollection 2014.
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.
热休克蛋白(HSPs)是保护蛋白质免受损伤的分子伴侣。HSP27的表达与癌症转化和侵袭相关。银杏叶提取物(EGb761)是销售最广泛的草药补充剂,具有抗血管生成作用并诱导肿瘤凋亡。关于EGb761对HSP表达影响的数据有限,尤其是在癌症方面。通过实时PCR、蛋白质印迹法和免疫组织化学检测了64例非小细胞肺癌(NSCLC)患者配对肿瘤组织和正常肺组织中的HSP27表达。使用NSCLC细胞系(A549/H441)检测体外迁移能力。NSCLC组织中HSP27表达高于正常肺组织。Kaplan-Meier生存分析表明,HSP27表达率低(<1)的NSCLC患者生存时间显著长于高表达率(>1)的患者(p = 0.04)。EGb761抑制A549/H441细胞的HSP27表达和迁移能力,这与HSP27-siRNA转染效果相同。此外,EGb761处理激活了AKT和p38信号通路,且不影响PI3K、ERK和JNK信号通路的表达。HSP27是NSCLC预后不良的指标。EGb761可能通过激活AKT和p38 MAPK信号通路抑制HSP27表达,从而降低A549/H441的迁移能力。