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Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells are heterogeneous and require high concentration of functional glucocorticoid receptors

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World Journal of Gastroenterology 2005年第40期11卷 6373-6380页

作者： Yen-Shen Lu Huang-Chun Lien Pei-Yen Yeh Kun-Huei Yeh Min-Liang Kuo Sung-Hsin Kuo Ann-Lii Cheng Department ofOncology National Taiwan University Hospital Graduate Instituteof Clinical Medicine National Taiwan University College ofMedicine Taipei Taiwan China Departments of Pathology National TaiwanUniversity Hospital Taipei Taiwan China Department of Oncology National Taiwan UniversityHospital Taipei Taiwan Department of Oncology and Departments of InternalMedicine National Taiwan University Hospital Departments ofInternal Medicine and Medical Research Far Eastern MemorialHospital Taipei Taiwan China Department of Oncology and Department ofInternal Medicine National Taiwan University Hospital TaipeiTaiwan China

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 ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin 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±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto 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

关键词： Glucocorticoids Glucocorticoid receptor Carcinoma Cell growth chemosensitivility Drug resistance

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