Inhibitory effect of the growth and hepatic metastasis in human colon carcinoma by all-trans retinoic acid

Abstract

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. Key words: All-trans retinoic acid; VEGF; Colon cancer; Hepatic metastasis; Microvessel density