Glucose-regulated protein 94 modulates the therapeutic efficacy to taxane in cervical cancer cells

被引：10

作者：

Tai, Cheng-Jeng

Wang, Jin-Wun ^{[3
]}

Su, Hou-Yu ^{[4
]}

Tai, Chen-Jei

Wang, Chien-Kai ^{[1
,2
,5
,6
]}

Wu, Chun-Te ^{[7
,8
]}

Lien, Yung-Chang ^{[10
,12
]}

Chang, Yu-Jia ^{[9
,10
,11
,13
,14
]}

机构：

[1] Taipei Med Univ Hosp, Dept Internal Med, Div Hematol & Oncol, Taipei, Taiwan

[2] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei, Taiwan

[3] Chiali Chi Mei Med Ctr, Dept Orthoped, Tainan, Taiwan

[4] St Marys Hosp Luodong, Dept Surg, Luodong, Yilan County, Taiwan

[5] Taipei Med Univ Hosp, Dept Chinese Med, Taipei, Taiwan

[6] Taipei Med Univ, Sch Med, Dept Obstet & Gynecol, Coll Med, Taipei, Taiwan

[7] Chang Gung Univ, Coll Med, Taipei, Taiwan

[8] Chang Gung Mem Hosp, Dept Urol, Keelung, Taiwan

[9] Taipei Med Univ, Grad Inst Clin Med, Coll Med, Taipei, Taiwan

[10] Taipei Med Univ, Dept Surg, Coll Med, Taipei, Taiwan

[11] Taipei Med Univ Hosp, Dept Surg, Taipei, Taiwan

[12] Taipei Med Univ Hosp, Div Chest Surg, Dept Surg, Taipei, Taiwan

[13] Taipei Med Univ, Ctr Excellence Canc Res, Taipei, Taiwan

[14] Taipei Med Univ & Hosp, Canc Res Ctr, Taipei 110, Taiwan

来源：

TUMOR BIOLOGY | 2014年 / 35卷 / 01期

关键词：

GRP94; Taxane; Chemoresistant; Cervical cancer; ETOPOSIDE-INDUCED APOPTOSIS; HEAT-SHOCK PROTEINS; BREAST-CANCER; COLON-CANCER; T-CELLS; GRP94; CHEMOTHERAPY; EXPRESSION; CARCINOMA; GRP78;

D O I：

10.1007/s13277-013-1056-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cervical cancer is an important health issue for women worldwide, and the endoplasmic reticulum stress pathway is important for determining the chemotherapeutic response to cancer. However, the role of glucose-regulated protein 94 (GRP94) in taxane therapy for cervical cancer remains unclear. In this study, we generated GRP94 knockdown (GRP94-KD) Hela cells using short hairpin RNAs and found that GRP94-KD cells were resistant to taxane treatment in an MTT assay. Scrambled control cells demonstrated higher levels of apoptosis when treated with taxanes in comparison to GRP94-KD cells, as determined by cell cycle profiling, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Caspase 3 and caspase 7 activity was also higher in scrambled control cells treated with taxane in comparison to GRP94-KD cells. Moreover, we found that depletion of GRP94 altered the levels of the apoptosis-related proteins Bcl2 and Bad, leading to sensitivity to taxane. Exposure to taxane also induced the expression of Bad in scrambled cells but not in GRP94-KD cells. In addition, the expression of Bcl2 was increased dramatically in GRP94-KD cells, whereas only a small increase was observed in scrambled cells. Therefore, we conclude that silencing GRP94 may increase resistance to taxane treatment in cervical cancer cells by altering the activation of the apoptosis pathway. In addition, GRP94 may represent a key biomarker for determining the therapeutic efficacy of taxane treatment in cervical cancer patients.

引用

页码：403 / 410

页数：8

共 36 条

[21] Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules [J].