作者pharmawind (Pharma Wind)
看板Pharmacy
标题Re: [药理] 抗癌药 bortezomib
时间Sat May 1 22:31:50 2010
※ 引述《gogoflower (万花筒)》之铭言：
: 想请问这药物的机制
: 书上说是抑制proteasome 但是这和cancer有什麽关系呢
: 我在网路上都找不到耶
: 有没有高手能解答
: 感谢 !!!!!
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.
简单来说~ 就是这样~
╔════════Ｙ═════Ｙ═════Ｙ═════Ｙ════════╗
║ ║
║
Bortezomib ║
║
IκB (紧抓不放) IκB ╮ ╱ ║
║ \
NF-κB │ ↙ Inhibit║
║
NF-κB ∣
╭┬┬ ┬┬╮ ║
║ ╲ ∣
NF-κB ╞ Proteosome ╡ ║
║ ╲↗ ↓ ＼
╞ 26S ╡ ║
║ ╭──────────╮
IκB(紧抓不放) ╰┴┴ ┴┴╯ ║
║ ∣ ∪∪∪∪ 细胞核 │ ｜ ║
║ ︱ ∩∩∩∩ │ ↓ ║
║ │
NF-κB │ ● o .0. ║
║ ╰─────↘────╯ ○‧○. ║
║ release Anti-apoptosis factors O。Ｏ. ║
║ ↘ ║
║
Tumor survival ║
╚═══════════════════════════════════╝
1.
NF-κB在细胞质中会被
IκB抓住而无法进入细胞核中，也就无法发号细胞生长
与抑制细胞凋亡的指令。
2. 而
Proteosome 26S是负责降解IκB的Enzyme
（牵涉到Ubiquitin, 略）。
3.
Bortezomib可抑制
Proteosome 26S，使得
IκB的量变多，进而使
NF-κB无法进
入细胞膜促进转录、发挥作用，便无法抵抗
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
如有错误 敬请各位前辈不吝指正
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※ 发信站: 批踢踢实业坊(ptt.cc)
◆ From: 118.170.206.15
1F：推 ayoun22:看到那张伟大的图，我哭了 05/01 23:41
※ 编辑: pharmawind 来自: 118.170.206.15 (05/01 23:50)
2F：推 IAMTHELAW:太强大了..要画很久吧 =.= 05/01 23:50
3F：推 danielh2o2:放进板画面!! 太强了!! 05/01 23:50
4F：→ pharmawind:的确是花了不少时间 下次我还是直接找图片圈一圈好了XD 05/01 23:50
5F：→ pharmawind:PS.细胞核里面那堆U是DNA，虽然它长的很不像双股螺旋XD 05/01 23:52
6F：推 philman:疯了吗....推专业 05/02 01:10
7F：推 happyheaven:看到图...不推不行 05/02 10:11
8F：推 imame:不推不行~~~~~~实在太威了你!!!!!!! 05/02 11:05
9F：推 sharkimage:强者 05/03 11:06
10F：推 fiaoms:强大！ 05/03 20:44
11F：推 sunnybluesky:推 05/04 08:35
12F：推 dnmay:原PO强者 05/04 14:18
13F：推 GongPii:赞XD 05/04 18:12
14F：推 Jamie653:看到学长推一下 05/07 19:14
15F：推 carters:......鬼....鬼神啊～～～～（跪） 05/10 00:47
16F：推 hikitsu:图中是否要改为"26S"proteosome? 05/12 16:39
17F：推 hikitsu:另外anti-apoptosis和growth应为两条不同的pathway 05/12 16:43
18F：→ hikitsu:可同时存在但并非上下游之关系 05/12 16:44
19F：→ hikitsu:将"growth"改为"survival"比较恰当 05/12 16:46
20F：→ hikitsu:更正上面，应为proteasome才对 05/12 16:50
※ 编辑: pharmawind 来自: 118.170.193.62 (05/12 23:06)
21F：→ pharmawind:感谢hikitsu指正 m(＿ ＿)m 受教了~ ^^ 05/12 23:06
22F：推 deri1800:强者........ 05/15 21:52
23F：推 stagger:学长我看不懂XDD 05/24 00:22
※ 编辑: pharmawind 来自: 118.170.199.11 (09/19 01:00)