Effect of Transfection with Human Interferon-β Gene Entrapped in Cationic Multilamellar Liposomes in Combination with 5-Fluorouracil on the Growth of Human Esophageal Cancer Cells

将重组人干扰素-β（hIFNβ）基因包埋于阳离子多层脂质体（IAB-1）中，分别注射于人食管癌细胞系WSSC的裸鼠皮下移植瘤内，观察其单独及与肿瘤抑制剂联合应用的抗肿瘤活性。注射后24小时和48小时收获肿瘤，并通过ELISA定量肿瘤内hIFNβ的浓度。hIFNβ仅在用IAB-1处理的小鼠中检测到，表明hIFNβ的产生是基因转染的结果。即使联合治疗，也仅观察到较弱的抗增殖作用。然后通过瘤内IAB-1、放射（在第1天单次加强2戈伊）以及IAB-1和放射的组合处理异种移植物。虽然单独放射治疗效果甚微，但放射和IAB-1联合治疗显示出惊人的抗增殖作用，疾病稳定超过3周。与对照小鼠相比，在任何治疗组中均未观察到显著体重减轻方面的不良反应。本研究结果将为IAB-1在局部晚期食管癌患者中的临床应用提供有价值的信息。

Antiproliferative potencies of humanrecombinantinterferon-β(hIFNβ) geneentrappedin cationic multilamellar liposomes (IAB-1) alone and in combination with antineoplastic agentswasevaluated, using a human esophageal cancer xenograft in vivo.hIFNβ or IAB-1 were injected into the subcutaneous tumor derived from a human esophageal cancer cell line, WSSC, in the dorsal flank of nude mice. Tumors were harvested 24 hours and 48 hours following the injection, and intratumoral concentrationof hIFNβ was quantified by ELISA. hIFNβ was detectable only in mice treated with IAB-1, suggesting that the production of hIFNβ as a result of gene transfection actually took place.Xenografts were then treated by intratumoral injection of IAB-1 alone and in combination with intraperitoneal 5FU or oral S-1,all at appropriatedoses. Onlyweak antiproliferative effects were observed, even with the combined treatments. Xenografts were then treated by intratumoral IAB-1, radiation (a single boost of 2 Gy on day 1), and a combination of IAB-1 and radiation. Although the treatment with radiation alone had little effect, a combination with radiation and IAB-1 exhibited an astonishing antiproliferative effect and the disease was stabilized for morethan 3 weeks. No adverse reaction in terms of significant body weight loss was observed in any of the treatment groups in comparison with the control mice. Current findings will become valuable information for clinical application of IAB-1 for patients with locally advanced esophageal cancer.