作者pharmawind (Pharma Wind)
看板Pharmacy
標題Re: [藥理] 抗癌藥 bortezomib
時間Sat May 1 22:31:50 2010
※ 引述《gogoflower (萬花筒)》之銘言：
: 想請問這藥物的機制
: 書上說是抑制proteasome 但是這和cancer有什麼關係呢
: 我在網路上都找不到耶
: 有沒有高手能解答
: 感謝 !!!!!
The proteasome is an enzyme complex that is responsible for degrading
proteins that control the cell cycle. Some of the proteins degraded by
proteosomes regulate critical functions for cancer growth, such as
regulation of the cell cycle, transcription factors,
apoptosis,
angiogenesis, and cell adhesion.
One proteosome inhibitor, bortezomib, is commercially available.
Bortezomib has very specific affinity for the catalytic portion of the
proteosome.It can induce apoptosis in cancer cells indirectly.
Bortezomib is a
specific inhibitor of the 26S proteasome; one consequence
of 26S proteasome inhibition is the accumulation of IκB, an inhibitor of
the major transcription factor NF-κB. NF-κB induces transcription of genes
that block cell death pathways and promote cell proliferation. Its activity
depends on its release from its inhibitory partner protein, IκB, in the
cytoplasm and move to the nucleus. When IκB fails to degrade, through the
actions of bortezomib, NF-κB remains in the cytoplasm, preventing it from
transcribing the genes that promote cancer growth.
簡單來說~ 就是這樣~
╔════════Ｙ═════Ｙ═════Ｙ═════Ｙ════════╗
║ ║
║
Bortezomib ║
║
IκB (緊抓不放) IκB ╮ ╱ ║
║ \
NF-κB │ ↙ Inhibit║
║
NF-κB ∣
╭┬┬ ┬┬╮ ║
║ ╲ ∣
NF-κB ╞ Proteosome ╡ ║
║ ╲↗ ↓ ＼
╞ 26S ╡ ║
║ ╭──────────╮
IκB(緊抓不放) ╰┴┴ ┴┴╯ ║
║ ∣ ∪∪∪∪ 細胞核 │ ｜ ║
║ ︱ ∩∩∩∩ │ ↓ ║
║ │
NF-κB │ ● o .0. ║
║ ╰─────↘────╯ ○‧○. ║
║ release Anti-apoptosis factors O。Ｏ. ║
║ ↘ ║
║
Tumor survival ║
╚═══════════════════════════════════╝
1.
NF-κB在細胞質中會被
IκB抓住而無法進入細胞核中，也就無法發號細胞生長
與抑制細胞凋亡的指令。
2. 而
Proteosome 26S是負責降解IκB的Enzyme
（牽涉到Ubiquitin, 略）。
3.
Bortezomib可抑制
Proteosome 26S，使得
IκB的量變多，進而使
NF-κB無法進
入細胞膜促進轉錄、發揮作用，便無法抵抗
apoptosis signal。
Bortezomib is approved for the treatment of patients with
multiple myeloma
and
mantle cell lymphoma.
Ref:
Pharmacotherapy- A Pathophysiologic Approach, 7th ed, 2008;17:2107
如有錯誤 敬請各位前輩不吝指正
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◆ From: 118.170.206.15
1F：推 ayoun22:看到那張偉大的圖，我哭了 05/01 23:41
※ 編輯: pharmawind 來自: 118.170.206.15 (05/01 23:50)
2F：推 IAMTHELAW:太強大了..要畫很久吧 =.= 05/01 23:50
3F：推 danielh2o2:放進板畫面!! 太強了!! 05/01 23:50
4F：→ pharmawind:的確是花了不少時間 下次我還是直接找圖片圈一圈好了XD 05/01 23:50
5F：→ pharmawind:PS.細胞核裡面那堆U是DNA，雖然它長的很不像雙股螺旋XD 05/01 23:52
6F：推 philman:瘋了嗎....推專業 05/02 01:10
7F：推 happyheaven:看到圖...不推不行 05/02 10:11
8F：推 imame:不推不行~~~~~~實在太威了你!!!!!!! 05/02 11:05
9F：推 sharkimage:強者 05/03 11:06
10F：推 fiaoms:強大！ 05/03 20:44
11F：推 sunnybluesky:推 05/04 08:35
12F：推 dnmay:原PO強者 05/04 14:18
13F：推 GongPii:讚XD 05/04 18:12
14F：推 Jamie653:看到學長推一下 05/07 19:14
15F：推 carters:......鬼....鬼神啊～～～～（跪） 05/10 00:47
16F：推 hikitsu:圖中是否要改為"26S"proteosome? 05/12 16:39
17F：推 hikitsu:另外anti-apoptosis和growth應為兩條不同的pathway 05/12 16:43
18F：→ hikitsu:可同時存在但並非上下游之關係 05/12 16:44
19F：→ hikitsu:將"growth"改為"survival"比較恰當 05/12 16:46
20F：→ hikitsu:更正上面，應為proteasome才對 05/12 16:50
※ 編輯: pharmawind 來自: 118.170.193.62 (05/12 23:06)
21F：→ pharmawind:感謝hikitsu指正 m(＿ ＿)m 受教了~ ^^ 05/12 23:06
22F：推 deri1800:強者........ 05/15 21:52
23F：推 stagger:學長我看不懂XDD 05/24 00:22
※ 編輯: pharmawind 來自: 118.170.199.11 (09/19 01:00)