Effects of ISO-1 on liver metastasis of mouse colonic cancer / 中华普通外科杂志

ABSTRACT

Objective To investigate the effects of ISO-1, a selective MIF tautomerase activity inhibitor, on liver metastasis in a BALB/c mouse model of colonic cancer. Methods Micmporous migration assay was used to determine the effect of ISO-1 on the invasion abilities of CT26 cells. Orthotopic transplantation of fresh colonic tumor fragments into the hernial sac of cecum was used in a BALB/c mouse model of eolorectal cancer. Thirty mouse models were divided into three groups and treated respectively with ISO-1 (0. 2 ml, 20 mg/kg), 5% DMSO and NS ( normal sodium) twice a week, iutraperitoneally. After 4 weeks, mice were sacrificed and the whole livers were made into serial slices to detect the occurrence of liver metastasis. Serum MIF tautomerase activities were measured using L-dopachrome methyl ester, ELISA was used to test serum VEGF concentrations. Immunohistochemical staining of CD31 was used for comparing microvascular density (MVD) of tumor tissues. Results 100 μmol/L ISO-1 treatment for 24 hours significantly reduced the average number of the cells penetrating polycarbonates, ( 151 ± 19 ) vs. ( 178 ± 9 ), P<0. 01. Serum MIF tautomerase activities were significantly inhibited after ISO-1 treatment (51% vs. 81%, P <0. 01 ). Compared with DMSO and NS treatment, ISO-1 decreased the occurrence of liver metastasis ( 10% ,60% and 70% ,respectively;x2 = 8. 30, P < 0. 05 ). Also ISO-1 decreased serum VEGF levels ( 15 ± 7 ) pg/ml, ( 63 ± 11 ) pg/ml and ( 67 ± 8 ) pg/ml, respectively; P < 0. 01 and the MVD of tumor tissues (17±4) ,(36±7) and( 38±5) ,respectively; P<0. 01. Conclusion In vitro ISO-1 inhibits the invasion ability of CT26 cells. In vivo ISO-1 reduces the occurrence of liver metastasis, possibly by a mechanism of inhibiting MIF tautomerase activities, down-regulating the expression of VEGF and reducing MVD.