皮質類固醇影響上皮細胞癌生長及化學藥物敏感性機轉之研究並探討與癌細胞反應模式相關之分子分類(1/3)
Other Title
Studies on the mechanisms of glucocorticoids on the growth and drug
sensitivity of carcinomas, and exploring relevant molecular classification(1/3)
sensitivity of carcinomas, and exploring relevant molecular classification(1/3)
Date Issued
2003
Date
2003
Author(s)
鄭安理
DOI
912314B002166
Abstract
Objectives: Glucocorticoids (GCs) are
commonly co-administered with anti-cancer
drugs such as cisplatin to prevent
drug-induced allergic reaction, nausea, and
vomiting. But little is known regarding the
effects of GCs on the growth and
chemosensitivity of common carcinomas
cells. Methods: Fourteen carcinoma cell lines
representing breast (MCF-7, MCF-7/MXR1,
MCF-7/TPT300), gastric (AGS, N87,SNU1),
lung (H460), cervical (SiHa, HeLa, Caski),
liver (Hep3B, Hut7), and nasopharyngeal
(NPC-TW01, NPC-TW04) cancer were
selected to assess the effects of
dexamethasone (DEX) on the cell growth
and cisplatin chemosensitivity of common
human cancers. Results: DEX had mutually
exclusive effects on either growth or cisplatin
sensitivity in 7 of the 14 cell lines. DEX
inhibited cell growth of 4 (MCF-7,
MCF-7/MXR1, MCF-7/TPT300, and HeLa),
increased cisplatin cytotoxicity of one (SiHa),
and decreased cisplatin cytotoxicity of 2
(H460 and Hep3B) cells lines. Although the
effect of DEX on these carcinoma cells was
unexpectedly diverse, it remained GC
receptor (GCR) dependent. The GCR
contents of the 7 cell lines affected by DEX
were significantly higher than those of the
other 7 cell lines unaffected by DEX (5.2 ±2.5 ×10 4
vs 1.3 ±1.4 ×10 4 , P=0.005).Only two
DEX-unresponsive cell lines (NPC-TW01
and NPC-TW04) had GCR contents at the
high range as those of the 7 DEX-responsive
cell lines. On further examination, the
function of the endogenous GCR of these
two cell lines was found to be impaired.
Further, transfection and expression of a
vector encoding GCR to AGS, a GCR
low-expressing and GC non-responsive cell
line, increased its susceptibility to DEX
manifested as an increased resistance toward
cisplatin. The cytotoxicity-enhancing effect
of GC in SiHa cells correlated well with its
effect on abrogating the cisplatin-induced
activation of NF-B. Expression of a
dominant-negative truncated I B gene in
SiHa cells completely abolished the
cytotoxicity-enhancing effect of DEX.
Conclusions: GCs may affect growth or
chemosensitivity of carcinoma cells
containing high concentration of functional
GCR. Although the effects are heterogeneous
and currently unpredictable , our data
underscore the importance of clarifying the
impact on tumor control by the
co-administed GCs to carcinoma patients
receiving chemotherapy. It is mandatory to
identify the molecular and cellular markers
that help predict the diverse effect of GCs on
carcinoma cells.
Subjects
Glucocorticoids
Glucocorticoid
receptor
receptor
Carcinoma
Cell growth
Chemosensitivity
Drug resistance
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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