الملخص
Objective To analyze the effect of siRNA targeting MIF( MIFsiRNA) on the growth of colorectal cancer xenografts and the life quality of tumor-bearing mice.Methods BALB/C mouse model carring colorectal cancer was established.Thirty mice were divided into three groups randomly and managed respectively with intratumor injection of DEPC water, MIFsiRNA(0.15 nmol/g) and non-specific siRNA (0.15 nmol/g), respectively twice a week for consecutively 4 weeks.Drinking water, fodder consumed and body weight was recorded daily, and tumor volume was measured once a week.Mice were sacrificed after four weeks.ELISA and immunohistochemistry were used to detect the expression of MIF in serum and in tumor tissues.Spectrophotometric detection was used to detect caspase-3 protein.TUNEL was used to detect apoptotic cells.Results MIF expression in serum in MIFsiRNA group was lower than the other two groups [(22 ± 6) ng/ml vs (32 ± 8) ng/ml and (33 ± 8) ng/ml, P ＜ 0.01]; MIF expression in tissues was less than the other two groups [(85 ± 20) /500 vs.(423 ± 23) /500 and (442 ± 31) /500, P ＜ 0.01]; Tumor was smaller than the other two groups at third and fourth week (P ＜ 0.01) ; Tumor weight was significantly less than the other two groups [(1.93 ±0.21) g vs (4.40 ±0.30) g and (5.25 ±0.44) g, P＜0.01]; Mice in MIFsiRNA group were healthier than the other two groups as judged by water and fodder consumption (P ＜ 0.01 ) , while weight change was not significantly different among the three groups ( P ＞ 0.05 ).Caspase-3 protein in tissues was higher than the other two groups [(0.74 ±0.06) μg vs (0.57 ±0.08) μg and (0.56 ±0.02) μg, P ＜0.01]; Apoptosis cells in tissues were higher than the other two groups [(12 ± 2)/ 100 个vs 0 and 0, P ＜ 0.01].Conclusions Knockdowning MIF gene expression inhibits the growth of colorectal cancer xenografts and improves life quality of tumor-bearing mice, possibly by a mechanism in which MIFsiRNA activates caspase-3 promoting cell apoptosis.
الملخص
The liver is the most common site of distant metastasis of colorectal cancer. In order to study colorectal cancer metastasis to the liver, establishing and choosing appropriate mouse model is crucially im-portant. In this review, we mainly discuss the mouse models of colorectal cancer and liver metastases: Tumor fragments or cancer cells orthotopic transplant to eoloncecal part, injecting cancer cells into the spleen, portal injection of cancer cells, colorectal cancer implantation to the subcapsular of the liver.