Abstract:
Objective This project aimed to compare the efficacy and toxicity of anti-tumor drugs, PDOX and DOX, on orthotop -ic nude mice model of human gastric carcinoma (GC).
Methods The orthotopic nude mice model of human GC was established with human GC cell line MGC- 803. The animals were randomized into PDOX (n=12), DOX (n=12), and Control (n=11) groups, and were treated with PDOX (28.8 mg/Kg, i.p), DOX (DOX4.0 mg/kg, i.p), and the control (10.0 ml/kg, i.p), respectively, on days10, 17, and 24. Detailed records of the general status were made on all animals twice a week. The experiments were terminated when the nude mice of any group died of tumor progression, and all the remaining nude mice were euthanized. Peripheral blood was collected for hematolo-gy and biochemistry. At autopsy, detailed records were made on the weight and size of GC, ascites, abdominal lymph nodes metastasis, and tumor-host body weight ratio. Histo-pathological studies were performed to identify any suspected sites. All data were subjected to statistical analysis.
Results Compared with the Control group, both the PDOX and DOX groups showed significant reduction in tumor weight and volume (P < 0.05), and both treatments resulted in weight reduction of gastric tumor by 26.4% and 24.9%, respectively. There were no statistical differences between the PDOX and DOX treatments (P>0.05). Based on peripheral blood routine, there was a significantly higher level of platelets in the PDOX than in the Control group and (P < 0.05), while lymphocyte ratio was lower in the PDOX than in the Control group (P < 0.05). There were no significant differences in red blood cells and hemoglobin levels among the three groups (P>0.05). There were also no significant differences in the liver and kidney functions among the three groups (P>0.05). Cardiac function showed that PDOX had a significantly higher level of CK-MB compared with the Control group (P < 0.01), and both the DOX and PDOX groups had no significant differences in creatine kinase (CK) and lactate dehydrogenase (LDH). Immunohistochemistry showed that PDOX had a significantly lower level of Ki-67 compared with the DOX and Control groups (P < 0.01). There were no statistically significant differences among Bcl-2, Bcl-6, Tunel, and VEGF of the groups (P>0.05). The values of CD34 and D2-40 decreased in the PDOX group compared with DOX and Control groups.
Conclusion Compared with DOX, PDOX may have a better overall efficacy in this GC model, particularly in terms of inhibiting distant metastases and reducing toxicities.