Abstract：
Combining phytochemicals and nanotechnology to improve the unfavorable innate properties of phytochemicals and develop them into potent nanomedicines to enhance antitumor efficacy has become a novel strategy for cancer chemoprevention. Melanoma is the most aggressive, metastatic, and deadly disease of the primary cutaneous neoplasms. In this study, we fabricated phytoconstituent-derived zingerone nanoparticles (NPs) and validated their effects on cell adhesion and motility in melanoma B16F10 cells. Our data indicated that zingerone NPs significantly induced cytotoxicity and anti-colony formation and inhibited cell migration and invasion. Moreover, zingerone NPs dramatically interfered with the cytoskeletal reorganization and markedly delayed the period of cell adhesion. Our results also revealed that zingerone NPs-mediated downregulation of MMPs (matrix metalloproteinases) activity is associated with inhibiting cell adhesion and motility. We further evaluated the effects of zingerone NPs on Src/FAK /Paxillin signaling, our data showed that zingerone NPs significantly inhibited the protein activities of Src, FAK, and Paxillin, indicating that they play important roles in zingerone NP-mediated anti-motility and anti-invasion in melanoma cells. Accordingly, the phytoconstituent-zingerone NPs can strengthen the inhibition of tumor growth, invasion, and metastasis in malignant melanoma. Altogether, these multi-pharmacological benefits of zingerone NPs will effectively achieve the purpose of melanoma prevention and invasion inhibition.
摘要：
结合植物化学物质和纳米技术来改善植物化学物质的不利固有特性，并将其开发成有效的纳米药物以增强抗肿瘤功效已成为癌症化学预防的新策略。黑色素瘤是最具侵袭性的,转移性，和原发性皮肤肿瘤的致命疾病。在这项研究中,我们制造了植物成分衍生的姜酮纳米颗粒（NPs），并验证了它们对黑色素瘤B16F10细胞粘附和运动的影响。我们的数据表明，姜酮NP显着诱导细胞毒性和抗集落形成，并抑制细胞迁移和侵袭。此外，姜酮NP会极大地干扰细胞骨架的重组，并显着延迟细胞粘附期。我们的结果还表明，姜酮NPs介导的MMPs（基质金属蛋白酶）活性下调与抑制细胞粘附和运动有关。我们进一步评估了姜酮NP对Src/FAK/Paxillin信号传导的影响，我们的数据表明，姜酮NP显著抑制Src的蛋白质活性，FAK,和Paxillin,表明它们在姜酮NP介导的黑色素瘤细胞的抗运动和抗侵袭中起重要作用。因此，植物成分姜酮NPs可以增强对肿瘤生长的抑制作用，入侵,和恶性黑色素瘤的转移。总之,姜酮NPs的这些多药理作用将有效达到预防黑色素瘤和抑制侵袭的目的。
