视黄酸对胃癌细胞MGc80-3体内外转移能力的影响

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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%.? Objective To observe the effect of retinoic acid (ATRA) on the metastasis of gastric cancer cells in vitro and in vivo. Methods The gastric cancer cell line MGc80-3 was treated with 10-6 mol/L all-trans ATRA. With fresh amniotic membrane as a cell adhesion object, observe the adhesion ability of MGc80  3 cells. The activity of βglucuronidase (βG) was determined using phenolphthalein βglucuronide sodium salt as substrate. Scanning electron microscopy and transmission electron microscopy were used to observe the ultrastructure of cells. The mRNA expression of nm23 gene was measured by Northern blot. The effect of ATRA on the metastasis of gastric cancer cells was further observed in vivo using established human gastric cancer nude mouse liver metastasis model. Results After ATRA treatment, the adhesion capacity of gastric cancer cells increased at early stage, but there was no statistical significance. After 80 days of treatment, the ability of cells to adhere to amnion decreased significantly. ATRA can not only effectively reduce the activity of β-G in the cells, but also inhibit the exocytosis of β-G cells. The inhibition rates were 4135% and 3719%, respectively. After treatment with ATRA, the microvilli of the cells were shortened or even disappeared. The cell surface was blister-like; microfilaments increased and arranged neatly, showing polar distribution at both ends of the nucleus. In the ATRA-treated cells, the mRNA expression of nm23 gene was significantly reduced and the inhibition rate was 50%. ATRA can reduce the tumorigenesis rate of transplanted submucosal tumors by 16.7%, inhibit the growth of spleen xenografts and metastasize tumors in the spleen, and significantly inhibit hepatic metastasis of transplanted tumors, resulting in a reduction of hepatic metastasis rate in nude mice33  3%, the inhibition rate of metastasis reached 94%. ?
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