比較Sulindac， COX-2 inhibitors和Curcumin對大腸癌產生過程中的一系列基因變化的影響
Date Issued
2002
Date
2002
Author(s)
魏淑
DOI
902314B002220
Abstract
The “Vogelgram ” proposed by Vogelstein
and his colleagues, described the
adenoma-adenocarcinoma sequence, had
mentioned the adenomatous polyposis coli
(APC) gene mutation in the early stage of
colorectal carcinogenesis. Mutation of the
APC gene leads to abnormal epithelial
proliferation and differentiation. -catenin
can bind members of the Tcf/Lef family of
transcription factors and activate gene
transcription. C-MYC, cyclin D1 and matrix
metalloproteinase-7 (MMP-7) were found to
be the downstream targets of this
-catenin/Tcf-regulated transcription. It
appears that c-MYC activation is a direct
consequence of APC loss and thus a primary
cause of tumor cell proliferation. Aspirin
and/or nonsteroidal anti-inflammatory drugs
(NSAIDs) have been shown to reduce the
adenoma size and numbers in FAP patients.
Disease prevention is receiving more
attention in the developed country today.
The risk-benefit ratio for chemoprevention
of colorectal cancer would likely improve if
high-risk groups could be identified and less
side effect drugs could be used. COX-2
selective inhibitors and curcumin have less
side effects than sulindac but their effects on
colorectal cancer remained to be clarified.
This study was designed to first realize the
serial gene expression changes after sulindac
treatment, especially focusing on APC,
-catenin, TCF, cyclin D1, MMP-7, axin-2
and c-MYC; and to second compare the
anti-proliferation and apoptosis-inducing
ability of sulindac, curcumin and COX-2
inhibitor. The results of this study revealed
that Sulindac still remained the most
constant effective (anticancer) agents among
these three test compounds which has the
effects of inducing cancer cells apoptosis
and cell cycle paused at G1 phase effects.
Curcumin has the effects of inducing cancer
cells apoptosis and cell cycle paused at G2M
phase. Lonine (Etolodac), a COX-2 inhibitor,
has less apoptosis-inducing effects but can
pause the cell cycle in G1 phase. All these
effects were time and dose dependent. The
Northern blot results showed that only c-myc
expression decreased in HCT116 after
sulindac treated for 48 hours but no
significant changes of other genes. Further
study is indicated for confirming the results.
Subjects
Sulindac
COX-2 inhibitor
Curcumin
Colorectal carcinogenesis
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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