Sichuan Medical University, Luzhou, Sichuan 646 000, PR China.
Sichuan Medical University, Luzhou, Sichuan 646 000, PR China.
Int J Pharm. 2015 Dec 30;496(2):699-708. doi: 10.1016/j.ijpharm.2015.11.019. Epub 2015 Nov 10.
Gastric cancer is a highly lethal malignancy and its 5-year survival rate remains depressed in spite of multiple treatment options. Targeting drug delivery to tumor vasculature may be a promising strategy for gastric cancer therapy, for it can block the nutrition source of tumor and inhibit the metastasis and invasion in a certain extent. In present study, we have prepared the drug-targeting delivery system of peptide GX1-mediated anionic liposomes carrying adenoviral vectors (GX1-Ad5-AL), in which the tumor suppressor gene of PTEN was integrated into DNA of Ad5 and the GX1 peptide could play targeting role to vascular of gastric cancer. The inhibition ability of GX1-Ad5-AL to human gastric cancer cell lines (SGC-7901) and human umbilical vein endothelial cells (HUVEC) was evaluated by MTT assay. Further, the cell migration assay was carried out in transwell inserts and the cells uptaking of GX1-Ad5-AL was detected by confocal laser scanning microscopy. The experimental results indicated that the average cell proliferation inhibition rates resulted from the drug delivery system of GX1-Ad5-AL in SGC-7901 and HUVEC were 68.36% and 64.13%, respectively which were higher than that resulted from GX1 or Ad5-AL. Meanwhile, results of cell migration experiment demonstrated that GX1-Ad5-AL could significantly suppress the migration of gastric cancer cell of SGC-7901. Moreover, both the imaging from confocal laser scanning microscopy and the quantitative analysis of fluorescence intensity showed that, GX1-Ad5-AL was more easily uptaken by SGC-7901 cells, as compared to Ad5-AL. Therefore, the formulation of GX1-Ad5-AL was effective for enhancing the inhibition effect and suppressing the migration of gastric cancer vascular endothelial cells.
胃癌是一种高度致命的恶性肿瘤，尽管有多种治疗选择，但 5 年生存率仍然很低。将药物靶向递送到肿瘤血管可能是治疗胃癌的一种有前途的策略，因为它可以阻断肿瘤的营养来源，并在一定程度上抑制转移和侵袭。在本研究中，我们制备了肽 GX1 介导的带负电荷的脂质体靶向递送系统，携带腺病毒载体（GX1-Ad5-AL），其中 PTEN 肿瘤抑制基因被整合到 Ad5 的 DNA 中，GX1 肽可以发挥对胃癌血管的靶向作用。通过 MTT 法评估 GX1-Ad5-AL 对人胃癌细胞系（SGC-7901）和人脐静脉内皮细胞（HUVEC）的抑制能力。进一步通过 Transwell 小室进行细胞迁移实验，通过共聚焦激光扫描显微镜检测细胞摄取 GX1-Ad5-AL 的情况。实验结果表明，GX1-Ad5-AL 药物递送系统在 SGC-7901 和 HUVEC 中的平均细胞增殖抑制率分别为 68.36%和 64.13%，高于 GX1 或 Ad5-AL。同时，细胞迁移实验结果表明，GX1-Ad5-AL 可显著抑制 SGC-7901 胃癌细胞的迁移。此外，共聚焦激光扫描显微镜的成像和荧光强度的定量分析均表明，与 Ad5-AL 相比，GX1-Ad5-AL 更容易被 SGC-7901 细胞摄取。因此，GX1-Ad5-AL 的制剂可有效增强抑制作用并抑制胃癌血管内皮细胞的迁移。
