美國(guó)賓夕法尼亞大學(xué)醫(yī)學(xué)院的研究人員研制出了一種可選擇性殺滅癌細(xì)胞的藥物,，或能為肝癌的治療打開(kāi)一個(gè)新窗口,。相關(guān)論文發(fā)表在最新一期的《消化道》雜志上。
據(jù)研究人員介紹,，在試管和小鼠實(shí)驗(yàn)中,，他們將一種化學(xué)藥物包裹在分子大小的小泡中作為一種抗癌劑，成功實(shí)現(xiàn)了抑制癌細(xì)胞增長(zhǎng)并最終促其死亡的目的,。
這種被包裹在薄膜當(dāng)中的藥物名為C6-神經(jīng)酰胺,，是鞘脂類的中間代謝產(chǎn)物，天然存在于人體細(xì)胞質(zhì)膜中,，具有控制細(xì)胞新陳代謝,、促使細(xì)胞衰老的能力。但是,，自然情況下人體內(nèi)的神經(jīng)酰胺在癌細(xì)胞中的含量過(guò)低,，并不能起到殺滅的作用。脂質(zhì)的特殊性質(zhì)也決定了神經(jīng)酰胺并不能像普通藥物那樣能直接被輸送到病灶區(qū)域,。為了解決這一問(wèn)題,，研究人員才想出上述“藥物膠囊”的主意。借助納米技術(shù),，研究人員讓神經(jīng)酰胺套上了這種分子大小的蛋白質(zhì)薄膜“外套”,，這才使其相容性質(zhì)得到了改變。
負(fù)責(zé)該項(xiàng)目的賓夕法尼亞大學(xué)醫(yī)學(xué)院博士馬克·凱斯特說(shuō),，神經(jīng)酰胺療法本身就是作為一種化療的替代療法而設(shè)計(jì)的,，其優(yōu)點(diǎn)在于可針對(duì)某一具體區(qū)域的癌細(xì)胞發(fā)起攻擊,，殺滅區(qū)域明確且不會(huì)使健康細(xì)胞受損,。
動(dòng)物實(shí)驗(yàn)顯示，這種藥物能有效殺死癌細(xì)胞而不傷及正常細(xì)胞,，在小鼠實(shí)驗(yàn)中已被證明能有效治療乳腺癌和黑色素瘤,。當(dāng)其與常用抗癌劑結(jié)合使用時(shí)也并未發(fā)現(xiàn)毒副作用,。
研究人員發(fā)現(xiàn)，在針對(duì)肝癌細(xì)胞的實(shí)驗(yàn)中,，該藥物也能選擇性誘導(dǎo)腫瘤細(xì)胞死亡,。在對(duì)患有肝癌小鼠的實(shí)驗(yàn)中，該藥封閉了為腫瘤生長(zhǎng)提供營(yíng)養(yǎng)的血管,。而營(yíng)養(yǎng)的缺乏會(huì)使細(xì)胞組織中產(chǎn)生更多的神經(jīng)酰胺,，并最終導(dǎo)致癌細(xì)胞死亡。
肝癌是世界上第五大常見(jiàn)癌癥,，晚期患者存活率不到百分之五,，極具危害性，目前臨床上一般多采取手術(shù),、放化療以及肝移植療法,，但治愈率較低。（生物谷Bioon.com）
生物谷推薦原文出處：
Gut, 2010; DOI: 10.1136/gut.2010.216671
Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma
Hephzibah Rani S Tagaram1, Nicole A DiVittore2, Brian M Barth2, James M Kaiser2, Diego Avella1, Eric T Kimchi1, Yixing Jiang3, Harriet C Isom4, Mark Kester2, Kevin F Staveley-O'Carroll1
Background and objectives Hepatocellular carcinoma (HCC) affects an increasing number of people worldwide. The poor survival rate of patients with HCC is manifested by an aggressive and metastatic phenotype, as well as a poor response to common therapeutic strategies. The purpose of this study was to evaluate the efficacy of nanoliposomal C6-ceramide as an antineoplastic agent in an in vivo model of human HCC.
Methods The growth-arresting and pro-apoptotic properties of nanoliposomal C6-ceramide were first evaluated in vitro in human SK-HEP-1 cells by assessing cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation, cell cycle distribution and AKT phosphorylation. SK-HEP-1 cells were then engrafted subcutaneously into athymic nude mice and nanoliposomal C6-ceramide was administered by tail vein injection. Tumour size was monitored over time, followed by excision of tumours to evaluate tumour vascularisation, proliferation, apoptosis and cellular signalling.
Results Nanoliposomal C6-ceramide, but not ghost (no ceramide) nanoliposomes, induced apoptotic cell death of SK-HEP-1 cells in vitro, concomitant with an accumulation of cells in the G2 phase of the cell cycle and decreased phosphorylation of AKT. Systemic administration of nanoliposomal C6-ceramide to mice engrafted with SK-HEP-1 tumours reduced tumour vascularisation and proliferation, induced tumour cell apoptosis, decreased phosphorylation of AKT and ultimately blocked tumour growth.
Conclusions These studies show that nanoliposomal ceramide is an efficacious antineoplastic agent for the treatment of in vitro and in vivo models of human HCC.
