Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan 626-870, Republic of Korea.
Department of Korean Internal Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
Int J Med Sci. 2017 Sep 4;14(11):1101-1109. doi: 10.7150/ijms.20104. eCollection 2017.
Melanomas are fast growing high-mortality tumors, and specific treatments for melanomas are needed. Melanoma cells overexpress focal adhesion kinase (FAK) compared to normal keratinocytes, and we sought to exploit this difference to create a selectively lethal therapy. We combined gold nanoparticles (GNP) with antibodies targeting phosphorylated FAK (p-FAK). These conjugates (p-FAK-GNP) entered G361 melanoma cells and bound p-FAK. Treatment with p-FAK-GNP decreased the viability of G361 cells in a time dependent manner by inducing apoptosis. To maximize the preferential killing of G361 cells, non-thermal atmospheric pressure plasma was used to stimulate the GNP within p-FAK-GNP. Combined treatment with plasma and p-FAK-GNP showed much higher lethality against G361 cells than HaCaT keratinocyte cells. The p-FAK-GNP induced apoptosis over 48 hours in G361 cells, whereas plasma and p-FAK-GNP killed G361 cells immediately. This study demonstrates that combining plasma with p-FAK-GNP results in selective lethality against human melanoma cells.
黑色素瘤是生长迅速、死亡率高的肿瘤,因此需要针对黑色素瘤的特定治疗方法。与正常角质形成细胞相比,黑色素瘤细胞过度表达粘着斑激酶(FAK),我们试图利用这种差异来创造一种选择性致死疗法。我们将金纳米粒子(GNP)与针对磷酸化 FAK(p-FAK)的抗体结合。这些缀合物(p-FAK-GNP)进入 G361 黑色素瘤细胞并与 p-FAK 结合。用 p-FAK-GNP 处理可通过诱导细胞凋亡而在时间依赖性方式降低 G361 细胞的活力。为了最大限度地提高 G361 细胞的优先杀伤,使用非热常压等离子体来刺激 p-FAK-GNP 中的 GNP。与等离子体和 p-FAK-GNP 的联合治疗对 G361 细胞的杀伤率远高于 HaCaT 角质形成细胞。p-FAK-GNP 在 48 小时内诱导 G361 细胞发生凋亡,而等离子体和 p-FAK-GNP 则立即杀死 G361 细胞。本研究表明,将等离子体与 p-FAK-GNP 联合使用可导致针对人黑色素瘤细胞的选择性致死。