视黄酸对胃癌细胞MGc80-3体内外转移能力的影响

Effects of retinoic acid on metastatic ability of gastric cancer cells MGc80 3 in vivo and in vitro *

目的观察视黄酸（ＡＴＲＡ）对胃癌细胞体内外转移能力的影响．方法以１０－６ｍｏｌ／Ｌ全反式ＡＴＲＡ处理胃癌细胞株ＭＧｃ８０３．用新鲜羊膜作为细胞粘附对象，观察ＭＧｃ８０３细胞的粘附能力．以酚酞β葡糖醛酸苷钠盐为底物，测定β葡糖醛酸酶（βＧ）活性．扫描电镜和透射电镜观察细胞超微结构的变化．以Ｎｏｒｔｈｅｒｎｂｌｏｔ测定ｎｍ２３基因ｍＲＮＡ的表达水平．利用已建立的人胃癌裸小鼠肝转移模型进一步在体内观察ＡＴＲＡ对胃癌细胞转移能力的作用．结果经ＡＴＲＡ处理后胃癌细胞的粘附能力在早期有所升高，但没有统计学意义；处理８０ｄ后，细胞粘附于羊膜的能力显著下降．ＡＴＲＡ既能有效降低细胞内βＧ的活性，也能抑制细胞向外分泌βＧ，抑制率分别为４１３５％和３７１９％．经ＡＴＲＡ处理后细胞微绒毛缩短、甚至消失，细胞表面呈泡状突起；微丝增多，排列整齐，呈极性分布于细胞核两端．在ＡＴＲＡ处理的细胞中，ｎｍ２３基因的ｍＲＮＡ表达水平明显降低，抑制率为５０％．ＡＴＲＡ能使脾包膜下移植瘤的成瘤率降低１６７％，抑制脾移植瘤的生长和脾内肿瘤转移；并能显著抑制移植瘤的肝转移，使裸鼠的肝转移率降低３３３％，转移瘤数的抑制率达９４％．?

AIM To investigate the effects of retinoic acid on metaststic ability of gastric cancer cells MGc80 3. METHODS MGc80 3 cells were treated with 10 -6 mol/L all trans retinoic acid (ATRA). MGc80 3 cells' adhesive ability to amnion was measured, by using fresh amnion as adhesive object. The activity of β glucuronidase (β G) was assayed using phenolphthalein mono β glucosiduroronic acid as substrate. The changes of ultrastructure were observed by SEM and TEM. The expression of nm23 gene in mRNA level was detected by Northern blot and analysed by Fluor S TM multilmager and Multi Analyst System (Bio Rad). Furthermore, MGc80 3 cells' metastatic ability in vivo was investigated on the model of human gastric cancer with liver metastasis in nude mice. RESULTS After MGc80 3 cells were treated with ATRA, the adhesive ability to amnion was suppressed remarkablly, although statistically it was enhanced in significantly in early stage. β G activity was decreased both introcellularly and extrocelluarly. The inhibition rates were 41 35% and 37 19%, respectively. Microvilli were shortened, even disappeared and filaments strengthened, arranged around nuclei more orderly and polarizably. The expression of nm23 gene in mRNA level was decreased obviously, the inhibition rate being 50%. The tumorigenesis rate in spleen was decreased by 16 7%, tumor growth and local metastasis was inhibited, liver metastatic rate was decreased by 33 3%. The number of metastatic tumors, which were concentrated in the swelling liver of untreated nude mice, was decreased by 94%. CONCLUSION Retinoic acid can effectively suppress the metastatic ability of gastric cancer cells in vivo and in vitro .