Rapamycin是經(jīng)由一種復(fù)活島土壤中的細(xì)菌Streptomyces hygroscopicus所分離出的物質(zhì),，研究發(fā)現(xiàn)Rapamycin具有抗生素(殺死細(xì)菌),、免疫抑制及抗腫瘤的作用。目前,，美國(guó)食品與藥物管理局已經(jīng)核準(zhǔn)Rapamycin用作防止身體產(chǎn)生器官或骨髓移植排斥反應(yīng)的藥物,，同時(shí)也可以用于心臟支架的涂層中。
在一篇發(fā)表于4月1 日Cancer Research中的研究,，科學(xué)家們發(fā)現(xiàn)Rapamycin還可以防止煙草造成的小鼠肺部腫瘤發(fā)展,。
研究人員讓小鼠暴露于常見(jiàn)的煙草特殊致癌物質(zhì)一個(gè)星期，發(fā)現(xiàn)以rapamycin處理的小鼠,，體內(nèi)腫瘤的數(shù)量減少了百分之90，而且腫瘤大小減少了百分之74,。
Rapamycin是mTOR分子(mammalian Target of Rapamycin)抑制劑,。mTOR是一種激酶(serine/threonine kinase)，對(duì)于細(xì)胞分裂,、生長(zhǎng)扮演著重要的調(diào)節(jié)作用,，其主要功能為細(xì)胞增生訊號(hào)之傳遞，及細(xì)胞周期的進(jìn)行,。
mTOR分子接收來(lái)自上游(細(xì)胞膜表面生長(zhǎng)因子及其受體)的訊息,，它扮演著相當(dāng)重要的角色，mTOR分子活化后,，可以帶動(dòng)下游一系列的細(xì)胞訊息傳遞,，進(jìn)一步促使細(xì)胞產(chǎn)生分化或分裂,。而在腫瘤細(xì)胞，這樣的調(diào)節(jié)機(jī)制出現(xiàn)了異常,，導(dǎo)致腫瘤細(xì)胞不正常增生及分化不良,，因此，mTOR分子是抗癌藥物的理想目標(biāo),。
Rapamycin 已經(jīng)在實(shí)驗(yàn)室中被證實(shí)可抑制許多癌細(xì)胞的生長(zhǎng),，包括橫紋肌肉瘤、神經(jīng)母細(xì)胞瘤,、肺小細(xì)胞癌,、骨癌、胰臟癌,、乳癌,、攝護(hù)腺癌、白血病癌細(xì)胞及B細(xì)胞淋巴癌等,。
(資料來(lái)源 : biocompare)
部分英文原文：
Cancer Research 67, 3475-3482, April 1, 2007. Published Online First March 27, 2007;
Epidemiology and Prevention
Oral Consumption of Pomegranate Fruit Extract Inhibits Growth and Progression of Primary Lung Tumors in Mice
Naghma Khan1, Farrukh Afaq1, Mee-Hyang Kweon1, KyungMann Kim2 and Hasan Mukhtar1
1 Department of Dermatology and 2 Biostatistics and Medical Informatics, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin
Requests for reprints: Hasan Mukhtar, Department of Dermatology, University of Wisconsin-Madison, Medical Sciences Center, B-25, 1300 University Avenue, Madison, WI 53706. Phone: 608-263-3927; Fax: 608-263-5223; E-mail: [email protected] .
To develop novel mechanism-based preventive approaches for lung cancer, we examined the effect of oral consumption of a human achievable dose of pomegranate fruit extract (PFE) on growth, progression, angiogenesis, and signaling pathways in two mouse lung tumor protocols. Benzo(a)pyrene [B(a)P] and N-nitroso-tris-chloroethylurea (NTCU) were used to induce lung tumors, and PFE was given in drinking water to A/J mice. Lung tumor yield was examined on the 84th day and 140 days after B(a)P dosing and 240 days after NTCU treatment. Mice treated with PFE and exposed to B(a)P and NTCU had statistically significant lower lung tumor multiplicities than mice treated with carcinogens only. Tumor reduction was 53.9% and 61.6% in the B(a)P + PFE group at 84 and 140 days, respectively, compared with the B(a)P group. The NTCU + PFE group had 65.9% tumor reduction compared with the NTCU group at 240 days. Immunoblot analysis and immunohistochemistry were used to determine effect on cell survival pathways and markers of cellular proliferation and angiogenesis. PFE treatment caused inhibition of (a) activation of nuclear factor-B and IB kinase, (b) degradation and phosphorylation of IB, (c) phosphorylation of mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase 1/2, and p38), (d) phosphatidylinositol 3-kinase (p85 and p110), (e) phosphorylation of Akt at Thr308, (f) activation of mammalian target of rapamycin signaling, (g) phosphorylation of c-met, and (h) markers of cell proliferation (Ki-67 and proliferating cell nuclear antigen) and angiogenesis (inducible nitric oxide synthase, CD31, and vascular endothelial growth factor) in lungs of B(a)P- and NTCU-treated mice. Thus, our data show that PFE significantly inhibits lung tumorigenesis in A/J mice and merits investigation as a chemopreventive agent for human lung cancer. [Cancer Res 2007;67(7):3475–82]
