| Objective: To investigate the inhibitory effects and mechanism of 2-[(3-carboxy-l -oxopropyl) amino]-2-deoxy-D-Glucose (COPADG) on human esophageal carcinoma in nude mice, and study the antitumous effect of combining the COPADG with 5-FU, then obsreve influence of COPADG on the growth and physiologic function of the nude mice.Method: Established the models of human esophageal carcinoma Eca-109 in nude mice, the models were randomly divided into four groups: control group, COPADG group, 5-FU group and COPADG+5-FU group (CF). We observed the general station of the animals, measured the weight of animal, tumor, spleen and tumor volume, caculated the supression rate of tumor and spleen-index, and drawed the growth curve of tumors and animals. The tumor specimen, heart, lungs, brain, liver, spleen, stomach, intestine, kidneys were observed by HE staining. Peripheral blood cells (PBC), ALT and AST were counted. The expression of Bcl-2, caspase-3, PCNA, VEGF and MVD were detected by immunohistochemistry. The apoptotic cell rate in the eraly stage was assayed by flow cytometry. The ultrastruction of tumor cells was viewed by TEM.Results:1. The models of human esophageal carcinoma Eca-109 in nude mice were stable and successful.2. The growth rate of tumors was the fastest and the volume of the tumor was the largest in control group, and there was significant difference with 5-FU group, COPADG group and CF group (P<0.01). There was significant difference between 5-FU group with COPADG group and CF group (P<0.01). There was no significant difference between COPADG group and CF group.3. The supression rates of tumor in COPADG, 5-FU, and CF group were 54.16%, 38.78%, and 73.91% respectively. The supression rates of tumor in CF group was the highest, and 5-FU was the lowest.4. There was no significant difference between control and COPADG group, 5-FU and CF group in animal weights. The animal weights of 5-FU and CF group were extenuation and there was significant difference compared with control group (P<0.01). There were significant difference between 5-FU and CF group compared with COPADG and control group in spleen-index (P<0.01), and COPADG group had no significant difference compared with control group. The pathological changes of tumor tissue, hearts, lungs, brains, livers, spleens, stomach, intestine and kidneys were no obvious difference.5. The PBC, ALT, and AST in COPADG were as the same as control group, and had not influence on animals. The counts of PBC in 5-FU and CF group were decreased obviously, but ALT, AST were increased, and had significant different compared with control group (P<0.05). There was significant different between 5-FU and CF group (P<0.05).6. The expression of Bcl-2 in control group was higher than the others (P<0.01). The expression of Bcl-2 in COPADG group and 5-FU group was higher than CF group (P<0.01), and there was no significant difference between COPADG and 5-FU group. The expression of caspase-3 in control group was lower than the others (P<0.01), COPADG group and 5-FU group was lower than CF group (P<0.01), and there was no significant difference between COPADG and 5-FU group. The PCNA LI in control group was higher than the others (P<0.01). The PCNA LI in 5-FU group was higher than COPADG group and CF group (P<0.01), and there was no significant difference between COPADG and CF group. The expression of VEGF in control group was higher than the others (P<0.01). There was no significant difference among COPADG, CF and 5-FU group. The MVD in control group was higher than the others (P<0.01), 5-FU group was higher than COPADG and CF group (P<0.01), and there was no significant difference between COPADG and CF group.7. The apoptotic cell rates in the eraly stage in COPADG, 5-FU, CF group were 13.05%,12.65%, 13.23%, respectively, and had significant difference compared with control group (6.02%) (P<0.01).8. Typical apoptotic cells were found in COPADG, 5-FU, and CF group, apoptotic bodies were detected occasionally. There were no apoptotic cells in control group.Conclusion:1. COPADG can inhibit the growth of the human esophageal caricinoma in nude mice.2. COPADG had not influence on growth, weitht, organs, PBC, ALT, and AST of the animals.3. COPADG induced apoptosis of esophageal carcinoma cells by downregulating the expression of BCL-2 and upregulating the expression of caspase-3.4. COPADG can downregulate the expreeion of PCNA, and inhibit the proliferation activity of tumor cells.5. COPADG can downregulate the expression of VEGF, decreace MVD of the tumors. It ihibited neovascularization of human esophageal caricinoma in nude mice.6. COPADG cooperating with 5-FU can enhance anti-tumor effect. COPADG can reduce the influce of 5-FU on spleen, PBC, ALT, and AST of the animals.
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