美国宾夕法尼亚大学医学院的研究人员研制出了一种可选择性杀灭癌细胞的药物，或能为肝癌的治疗打开一个新窗口。相关论文发表在最新一期的《消化道》杂志上。

据研究人员介绍，在试管和小鼠实验中，他们将一种化学药物包裹在分子大小的小泡中作为一种抗癌剂，成功实现了抑制癌细胞增长并最终促其死亡的目的。

这种被包裹在薄膜当中的药物名为C6-神经酰胺，是鞘脂类的中间代谢产物，天然存在于人体细胞质膜中，具有控制细胞新陈代谢、促使细胞衰老的能力。但是，自然情况下人体内的神经酰胺在癌细胞中的含量过低，并不能起到杀灭的作用。脂质的特殊性质也决定了神经酰胺并不能像普通药物那样能直接被输送到病灶区域。为了解决这一问题，研究人员才想出上述“药物胶囊”的主意。借助纳米技术，研究人员让神经酰胺套上了这种分子大小的蛋白质薄膜“外套”，这才使其相容性质得到了改变。

负责该项目的宾夕法尼亚大学医学院博士马克·凯斯特说，神经酰胺疗法本身就是作为一种化疗的替代疗法而设计的，其优点在于可针对某一具体区域的癌细胞发起攻击，杀灭区域明确且不会使健康细胞受损。

动物实验显示，这种药物能有效杀死癌细胞而不伤及正常细胞，在小鼠实验中已被证明能有效治疗乳腺癌和黑色素瘤。当其与常用抗癌剂结合使用时也并未发现毒副作用。

研究人员发现，在针对肝癌细胞的实验中，该药物也能选择性诱导肿瘤细胞死亡。在对患有肝癌小鼠的实验中，该药封闭了为肿瘤生长提供营养的血管。而营养的缺乏会使细胞组织中产生更多的神经酰胺，并最终导致癌细胞死亡。

肝癌是世界上第五大常见癌症，晚期患者存活率不到百分之五，极具危害性，目前临床上一般多采取手术、放化疗以及肝移植疗法，但治愈率较低。

原文出处：

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.