Abu-Baker Shadi, Chu Zhengtao, Stevens Ashley M, Li Jie, Qi Xiaoyang
Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH ; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
J Cancer Ther. 2012 Aug;3(4):321-326. doi: 10.4236/jct.2012.34041.
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 and 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.
鳞状细胞癌(SCC)和黑色素瘤是人类皮肤恶性肿瘤,仅在美国,每年的死亡率就超过10000例。在本研究中,溶酶体蛋白鞘脂激活蛋白C(SapC)和磷脂二油酰磷脂酰丝氨酸(DOPS)被组装成癌症选择性纳米囊泡(SapC-DOPS),并在多种皮肤癌模型中成功进行了测试。使用MTT法测定细胞死亡百分比,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,即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,纳米囊泡通过诱导凋亡性细胞死亡选择性地杀死皮肤癌细胞,而未转化的皮肤细胞则不受影响。使用皮下皮肤肿瘤异种移植模型,皮下注射SapC-DOPS治疗的动物在治疗4天后,与对照组相比,肿瘤缩小了79.4%。正如通过异种移植肿瘤切片的TUNEL染色所显示的那样,与对照组相比,我们观察到纳米囊泡通过诱导凋亡性细胞死亡杀死皮肤癌细胞。