Brief Reports
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2005; 11(40): 6373-6380
Published online Oct 28, 2005. doi: 10.3748/wjg.v11.i40.6373
Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells are heterogeneous and require high concentration of functional glucocorticoid receptors
Yen-Shen Lu, Huang-Chun Lien, Pei-Yen Yeh, Kun-Huei Yeh, Min-Liang Kuo, Sung-Hsin Kuo, Ann-Lii Cheng
Yen-Shen Lu, Sung-Hsin Kuo, Min-Liang Kuo, Department of Oncology, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, China
Huang-Chun Lien, Departments of Pathology, National Taiwan University Hospital, Taipei, Taiwan, China
Pei-Yen Yeh, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
Kun-Huei Yeh, Department of Oncology, and Departments of Internal Medicine, National Taiwan University Hospital, Departments of Internal Medicine and Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan, China
Ann-Lii Cheng, Department of Oncology, and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by grants from the National Science Council No.NSC 93-2314-B-002-006, Taiwan, and grants from National Taiwan University Hospital 91-N006
Correspondence to: Ann-Lii Cheng, Department of Oncology, and Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan, China. andrew@ha.mc.ntu.edu.tw
Telephone: +886-2-23123456-7251 Fax: +886-2-23711174
Received: February 15, 2005
Revised: April 15, 2005
Accepted: April 18, 2005
Published online: October 28, 2005
Abstract

AIM: To determine how glucocorticoids (GCs) may affect the growth and chemosensitivity of common carcinoma cells.

METHODS: The effect of dexamethasone (DEX) on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors (GR) was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and cells were done by PA1-511A, an anti-GR monoclonal antibody.

RESULTS: DEX inhibited cell growth of four (MCF-7, MCF-7/MXR1, MCF-7/TPT300, and HeLa), increased cisplatin cytotoxicity of one (SiHa), and decreased cisplatin cytotoxicity of two (H460 and Hep3B) cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX (5.2±2.5×104 sites/cell vs 1.3±1.4×104 sites/cell, P = 0.005). Only two DEX-unresponsive cell lines (NPC-TW01 and NPC-TW04) contained high GR amounts in the range (1.9-8.1×104 sites/cell) of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was found to be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 (11.1%) breast cancer and 43 of the 85 (50.6%) non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines.

CONCLUSION: The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.

Keywords: Glucocorticoids; Glucocorticoid receptor; Carcinoma; Cell growth; Chemosensitivity; Drug resistance