In Vitro and In Vivo Antimetastatic Effect of Glutathione Disulfide Liposomes.
In Vitro and In Vivo Antimetastatic Effect of Glutathione Disulfide Liposomes.
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DOI：
10.1177/1179064417695255
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Guan X
中科院分区：
文献类型：
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作者：
Sadhu SS;Wang S;Dachineni R;Averineni RK;Seefeldt T;Xie J;Tummala H;Bhat GJ;Guan X
癌症转移是癌症死亡的主要原因。尽管进行了广泛的研究，但仍然缺乏有效的癌症转移治疗。癌转移涉及4个基本步骤：细胞脱离、迁移、侵袭和粘附。脱落是转移的第一步，也是必要的一步。谷胱甘肽二硫化物（GSSG）是由谷胱甘肽（GSH）氧化产生的，谷胱甘肽以毫摩尔浓度存在于生物系统中。虽然GSSG是可商购的，但GSSG对细胞功能/功能障碍的影响尚未得到充分研究，这是由于GSSG不是细胞膜可渗透的，并且缺乏特异性增加细胞中GSSG的方法。我们已经开发了GSSG脂质体，其有效地将GSSG递送至细胞。出乎意料的是，用GSSG脂质体处理的细胞对通过胰蛋白酶消化的脱离具有抗性。这一观察结果导致了GSSG脂质体的抗转移作用的研究。我们的数据表明，1 mg/mL的GSSG脂质体完全阻断细胞脱离和迁移，并显著抑制癌细胞侵袭。水性GSSG没有表现出这种作用，证实对细胞脱离、迁移和侵袭的影响是由GSSG的细胞内递送引起的。小鼠黑色素瘤实验转移模型的体内实验表明，GSSG脂质体可预防黑色素瘤肺转移。通过对分离和迁移的作用的独特抗转移机制以及有效的体外和体内转移抑制，保证了GSSG脂质体作为癌症转移的潜在治疗的进一步研究。
Cancer metastasis is the major cause of cancer mortality. Despite extensive research efforts, effective treatment for cancer metastasis is still lacking. Cancer metastasis involves 4 essential steps: cell detachment, migration, invasion, and adhesion. Detachment is the first and required step for metastasis. Glutathione disulfide (GSSG) is derived from the oxidation of glutathione (GSH), which is present in biological systems in millimolar concentration. Although GSSG is commercially available, the impact of GSSG on cell functions/dysfunctions has not been fully explored due to the fact that GSSG is not cell membrane permeable and a lack of method to specifically increase GSSG in cells. We have developed GSSG liposomes that effectively deliver GSSG to cells. Unexpectedly, cells treated with GSSG liposomes were resistant to detachment by trypsinization. This observation led to the investigation of the antimetastatic effect of GSSG liposomes. Our data demonstrate that GSSG liposomes at 1 mg/mL completely blocked cell detachment and migration, and significantly inhibited cancer cell invasion. Aqueous GSSG showed no such effect, confirming that the effects on cell detachment, migration, and invasion were caused by the intracellular delivery of GSSG. An in vivo experiment with a murine melanoma experimental metastasis model showed that GSSG liposomes prevented melanoma lung metastasis. The unique antimetastatic mechanism through the effects on detachment and migration, and effective in vitro and in vivo metastasis inhibition, warrants further investigation of the GSSG liposomes as a potential treatment for cancer metastasis.