维胺酸对体外转化人支气管上皮细胞及体内构建人支气管上皮组织的抑制作用

癌前改变是肿瘤演变过程中的关键阶段。许多研究显示维甲类化合物对动物肿瘤及体外恶性细胞系具有抑制作用，但尚未见其对肺癌前病变作用的实验室研究报道。人类肺癌的绝大部分起源于支气管上皮，为研究维胺酸对体外转化人支气管上皮M细胞系以及在大鼠气管构建后移植到裸鼠体内生长的具有癌前病变特点的人支气管上皮组织的抑制作用，采用上皮细胞无血清培养技术，人支气管上皮组织大鼠气管内构建／裸鼠皮下移植生长技术，流式细胞学分析，免疫组化、凋亡细胞原位末端标记以及病理学检查等研究方法发现，维胺酸可抑制体外培养的转化人支气管上皮细胞的增殖，使S期细胞比例下降，以及细胞增殖标志Ki-67、mpm-2阳性反应细胞比例下降；明显诱导细胞凋亡。裸鼠腹腔注射给予维胺酸也可使大鼠气管内构建后移植到裸鼠体内生长的癌前期人支气管上皮组织的生长率明显降低，病变程度明显减轻；同样可以诱导细胞凋亡。研究结果提示，维胺酸对体外培养的转化人支气管上皮细胞系及大鼠气管构建／裸鼠体内移植生长的人支气管上皮组织均有明显的抑制作用，是有希望的肺癌化学预防药物。

INHIBITORY EFFECTS OF N-(4-HYDROXYLPHENOL) RETINAMIDE ON TRANSFORMED HUMAN BRONCHIAL EPITHELIAL CELLS IN VITRO AND RECONSTRUCTED HUMAN BRONCHIAL EPITHELIUM IN VIVO

Precancerous lesion is one of most important steps in tumorigenesis. It has been shown that retinoids have reliable effects on controlling many kinds of animal tumor and malignant tumor cell lines in vitro, but there is no laboratory report on the biological effect of retinoids on the precancer-ous lesion of human lung cancer. In this study the methods including of cell serum-free culture, precancerous model of human bronchial epithelium reconstructed in rat trachea/ xeno-transplanted in nude mice, flowcytometry, im-munohistochemistry, TUNEL and pathological observation have been used to study the biological effects of N( 4-hydroxyphenol ) retinamide (4-HPR), one new kind of retinoids, on trans- formed human bronchial epithelial cells in vitro and premalignant human bronchial epithelium in vivo. The results showed that in the study in vitro, the proliferation of transformed human bronchial epithelial cells, the ratio of cells in S phase, and the percentage of cells that positively react to antibody Ki-67 and mpm-2 were inhibited, but apoptotic cells were induced significantly by 4-HPR exposure. At the experiment in vivo, both growth rates and precancerous grades of the reconstructed human bronchial epithelium were reduced, and apoptotic cells were also observed in epithelium after 4-HPR treatment. The results suggested that 4-HPR is one of hopeful chemo-preventive medicines to lung cancer.