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

利用人食管癌异种体内移植，研究了人重组干扰素-β(hifn -β)基因包载在阳离子多层脂质体（IAB-1）单独使用和与抗肿瘤药物联合使用的抗增殖能力。将hIFNβ或IAB-1注射到裸鼠背侧的人食管癌细胞系WSSC皮下肿瘤中。注射后24小时和48小时采集肿瘤，用ELISA法测定瘤内hIFNβ浓度。hIFNβ仅在IAB-1处理的小鼠中检测到，这表明hIFNβ的产生实际上是基因转染的结果。异种移植物分别在瘤内单独注射IAB-1，并联合腹腔注射5FU或口服S-1，均以适当剂量治疗。即使联合治疗，也只观察到微弱的抗增殖作用。然后异种移植物接受瘤内IAB-1、辐射（第1天单次增强2 Gy）以及IAB-1和辐射联合治疗。虽然单纯放射治疗效果甚微，但放射与IAB-1联合治疗显示出惊人的抗增殖效果，病情稳定了3周以上。与对照组小鼠相比，在任何治疗组均未观察到明显的体重减轻方面的不良反应。目前的研究结果将为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.