BCL-2與BAX基因表現對胃癌抗藥性之影響與其相關機制之研究
Date Issued
1999
Date
1999
Author(s)
鄭安理
DOI
882314B002052
Abstract
“ Apoptosis ” is the final common path-way
of most chemotherapy-induced tumor
cell death. Bcl-2 and Bax are two of the key
players regulating the apoptosis phenomenon.
Bcl-2 is a blocker of apoptosis, while Bax
functions as a promoter of apoptosis. In this
study, we examined the roles of Bcl-2 and
Bax in drug resistance of gastric cancer cells.
Bcl-2 and Bax protein expression were
determined by immunohistochemical stains
in 29 gastric cancer tissues, and correlated
with chemotherapy responses (13 responders
and 16 non-responders). Bcl-2 and Bax
protein expression was found in 10.3 ± 5.7%
and 72.4 ± 8.3% gastric cancer tissues,
respectively. However, In this group of
patients, we cannot find statistically
significant correlation between Bcl-2 or Bax
protein expression and chemotherapy
responses (P= 0.078 and 0.943 by Fisher
exact test, respectively).
In cell line studies, we have examined 7
human gastric cancer cell lines. All of them
had Bax expression, and 5 of them had Bcl-2
expression (except AGS and NCI-N87).
These two Bcl-2(-) parental gastric cancer lines were transfected with Bcl-2 cDNA expression vector, selected for stably trans-fected
clones, verified by Western blot, then
selected for further study. Compared with
the parental cell lines, the Bcl-2 transfectants
had 1.7- to 125-fold higher IC50 of multiple
structurally unrelated chemotherapeutic
agents, including 5-FU, cisplatin, doxo-rubicin,
etoposide, paclitaxel, and docetaxel.
We concluded that (1) Bax protein is
more frequently expressed than Bcl-2 in
gastric cancer tissues; (2) although we cannot
find statistically significant correlation
between Bcl-2 or Baxprotein expression and
HDFL-based chemotherapy responses, our in
vitro cell line model suggests that Bcl-2
overexpression may be a multidrug resistance marker of gastric cancer. This in vitro
model is potentially useful for searching of
Bcl-2 modulating agents, which may help
reverse drug resistance conferred by Bcl-2 overexpression.
Subjects
gastric cancer
drug resistance
apoptosis
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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