Cytotoxicity and Selectivity in Skin Cancer by SapC-DOPS Nanovesicles.
Cytotoxicity and Selectivity in Skin Cancer by SapC-DOPS Nanovesicles.
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DOI：
10.4236/jct.2012.34041
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Qi X
中科院分区：
文献类型：
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作者：
Abu-Baker S;Chu Z;Stevens AM;Li J;Qi X
鳞状细胞癌 (SCC) 和黑色素瘤是人类皮肤的恶性癌症，仅在美国每年的死亡率就超过 10,000 例。在这项研究中，溶酶体蛋白saposin C (SapC) 和磷脂二酰磷脂酰丝氨酸(DOPS) 被组装成癌症选择性纳米囊泡(SapC-DOPS)，并成功使用多种体外和体内皮肤癌模型进行了测试。使用测量细胞死亡百分比的 MTT 测定，将 SapC-DOPS 对三种皮肤肿瘤细胞系（鳞状细胞癌、SK-MEL-28 和 MeWo）的细胞毒性作用与两种正常非致瘤性皮肤细胞系（正常永生化角质形成细胞 (NIK) 和人成纤维细胞 (HFC)）进行比较。我们观察到，纳米囊泡通过诱导细胞凋亡来选择性杀死皮肤癌细胞，而未转化的皮肤癌细胞则不受影响。使用皮下皮肤肿瘤异种移植物，通过皮下注射 SapC-DOPS 治疗的动物在治疗 4 天后，与对照组相比，肿瘤减少了 79.4%。通过异种移植肿瘤切片的 TUNEL 染色显示，与对照相比，我们观察到纳米囊泡通过诱导细胞凋亡来杀死皮肤癌细胞。
Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceed 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4 % tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.