CAJ | 학술논문

目的观察全反式维甲酸(ATRA)对人结肠癌细胞生长及肝转移的抑制作用.方法 0、2、4、8μmol／LATRA分别作用于SW480/M5细胞48 h,免疫组织化学检测SW480/M5细胞血管内皮生长因子-A(VEGF-A)的表达水平.以SW480/M5细胞建立裸鼠原位肿瘤种植模型,随机分为5组,分别以生理盐水、溶剂对照液及5、15、45 mg/kg ATRA对裸鼠隔日灌胃,6周后观察裸鼠原位种植瘤及肝转移瘤的生长,实时荧光定量聚合酶链反应(RT-PCR)检测肿瘤组织VEGF-A mRNA表达水平,免疫组织化学检测裸鼠肿瘤组织微血管密度(MVD).结果 SW480/M5细胞VEGF-A阳性率随着ATRA作用浓度的增加逐渐下降,差异有统计学意义(x2=630.96,P＜0.01).各ATRA作用组原位肿瘤的抑瘤率为4.1％、31.6％及49.7％,肝转移发生率为63.6％、36.4％及20.0％,差异均有统计学意义(分别为P＜0.01及P＜0.05).与对照组比较,中剂量及高剂量组裸鼠原位肿瘤显著缩小(P＜0.05)、肿瘤肝转移程度明显降低(P＜0.05),肿瘤组织的VEGF-A mRNA水平及MVD值亦显著下降(P＜0.05).结论 ATRA能下调人结肠癌原位种植肿瘤和肝转移瘤组织VEGF-A的表达,减少肿瘤新生血管的形成,对结肠癌生长和肝转移具有抑制作用.
목적 관찰전반식유갑산(ATRA)대인결장암세포생장급간전이적억제작용.방법 0、2、4、8μmol／LATRA분별작용우SW480/M5세포48 h,면역조직화학검측SW480/M5세포혈관내피생장인자-A(VEGF-A)적표체수평.이SW480/M5세포건립라서원위종류충식모형,수궤분위5조,분별이생리염수、용제대조액급5、15、45 mg/kg ATRA대라서격일관위,6주후관찰라서원위충식류급간전이류적생장,실시형광정량취합매련반응(RT-PCR)검측종류조직VEGF-A mRNA표체수평,면역조직화학검측라서종류조직미혈관밀도(MVD).결과 SW480/M5세포VEGF-A양성솔수착ATRA작용농도적증가축점하강,차이유통계학의의(x2=630.96,P＜0.01).각ATRA작용조원위종류적억류솔위4.1％、31.6％급49.7％,간전이발생솔위63.6％、36.4％급20.0％,차이균유통계학의의(분별위P＜0.01급P＜0.05).여대조조비교,중제량급고제량조라서원위종류현저축소(P＜0.05)、종류간전이정도명현강저(P＜0.05),종류조직적VEGF-A mRNA수평급MVD치역현저하강(P＜0.05).결론 ATRA능하조인결장암원위충식종류화간전이류조직VEGF-A적표체,감소종류신생혈관적형성,대결장암생장화간전이구유억제작용.
Objective To evaluate the inhibitory effect of all-trans retinoic acid (ATRA) on the growth and hepatic metastasis of colon cancer.Methods SW480/M5 cells were treated with ATRA at 0,2,4,8 μmol/L for 48 hours respectively,Vascular endothelial growth factor A (VEGF-A) expression of SW480/M5 was determined by immunohistochemical analysis.The nude mice mode of orthotopic tumor implantation was established by SW480/M5.Sixty nude mice models were divided into five groups randomly,the nude mices were administered intragastrically once every two days with physiological saline,dissolvant and 5,15,45 mg/kg ATRA,respectively.The administration lasted 6 weeks,subsequently,growth of tumor masses and hepatic metastasis were observed,VEGF-A mRNA expression in both orthotopic and liver metastatic tumors were examined by Real-time polymerase chain reaction ( RT-PCR),in addition,the microvessel density (MVD) of tumor masses were measured by immunohistochemical staining.Results Immunohistochemical results showed that with the increasing concentrations of ATRA acting on SW480/M5 cells,The positive expression rates of VEGF-A in SW480/M5 cells were gradually decreased (x2 =630.96,P ＜0.01).Compared to tumor-bearing mice treated by physiological saline and dissolvant,the inhibitory rates of orthotopic tumor treated by ATRA increased to 4.1％,31.6％ and 49.7％ (P ＜0.01 ),with the liver metastatic rate decreased to 63.6％,36.4％ and 20.0％ (P ＜ 0.05 ).In addition,size and weight of orthotopic mass,extent of liver metastasis,as well as the expression of VEGF-A mRNA and the microvessel density of orthotopic or metastatic tumors,were significantly decreased in both 15 and 45 mg/kg ATRA groups (P ＜ 0.05 ).Conclusion ATRA has inhibitory effect on VEGF-A expression,angiogenesis,growth and hepatic metastasis of colon cancer.