| Objective:The incidence and mortality of pulmonary carcinoma are first rank in malignant tumor. Most pulmonary carcinoma patients lost the opportunity of surgery when they were clearly diagnosed. External irradiation combined with chemotherapy has become the method of the conventional treatment for advanced pulmonary carcinoma. For radiation dose of normal lung tissue's tolerance limits, the local control rate of tumor is still very low, the clinical efficacy of pulmonary carcinoma was poor, and the treatment causes serious side effects. At present,interstitial implantation radioactive seed in the treatment of prostate cancer and other solid tumors have achieved a certain effect. But in the treatment of pulmonary carcinoma, particularly, there are few studies of the radioactive seed implantation combined with chemotherapy. In the selection of the radioactive source ,the iodine-125 is the most commonly radioactive seed. Compared with external irradiation, it has many advantages: low strength of radioactive source, short distance of function, strong damage on tumor, small injury to normal tissue, high biological effect and thorough treatment. 125I Combined with chemotherapy has been confirmed which has less injury to normal tissue,significantly reduce the rate of local recurrence and distant metastasis was reduced in pancreatic cancer, head and neck cancer and other solid tumors. In the treatment of pulmonary carcinoma,it just start at the exploratory stage, that requires further study. Paclitaxel is one of the most effective new drugs to the pulmonary carcinoma. It makes microtubule polymerization , block cell karyokinesis, and produce large G2/M phase, which is a unique mechanism of microtubule polymerization. Moreover, the ray is the more sensitive to kill G2/M cell. So paclitaxel combined with the radioactive 125I seeds is reasonable in treatment. In this experiment, 125I combined with paclitaxel on Lewis pulmonary carcinoma in Kunming mice to research the anti-tumor effect and its mechanisms, and provide experimental evidence for further clinical application.Methods: 56 healthy Kunming mice were used to establish subcutaneous xenograft Lewis pulmonary carcinoma model. 36 successful model mice were randomly divided into control group and treated group, treated group include paclitaxel group,125I group and combined 125I with paclitaxel group. The number of mice in each group is 9. At 1st day, control group was given saline 0.025ml/g, paclitaxel group was given paclitaxel 0.5mg/g+saline0.025ml/g, 125I group were implanted iodine-125 seeds with a prescription dose of 120Gy, combined group were given paclitaxel 0.5mg/g+saline0.025ml/g and implanted iodine-125 seeds with a prescription dose of 120Gy. At the 8th day, control group and 125I group were given saline 0.025ml/g, meanwhile paclitaxel group and combined group were given paclitaxel 0.5mg/g+saline0.025ml/g. We observe the daily general and measure tumor volume every other day. At 30th day, draw tumor growth curve, calculate inhibition rate, assess tumor regression according to the Rectal Cabcer Regression Grade(RCRG) system of Wheeler. Pathological changes of tumor tissue were detected under light microscope. Apoptosis of rate was analyzed by flow cytometry. Expression of Caspase-9 and Caspase-3 protein in tumor tissue was detected by immunohistochemical staining.Results: 1.Changes of tumor volume: The tumor volume increases gradually in control group, and reach 2456mm3 at 30th day. The tumor volume was also on the rise in paclitaxel group, the volume was 1451mm3 at 30th day. The tumor volume in 125I and combined group showed a downward-increased trend. It gradually decreased after 10 days, and it was 418mm3,210mm3 respectively at 30 days. The tumor volume in combined group dropped most. 2. Inhibiting effects: Inhibiting rate of treated groups is 43.51%, 71.96%, 88.97%, respectively. There were a significant difference among treated groups(P<0.05) 3.Changes of pathologic histology: Compared with control group, histopathological changes in the treated group was statistically difference (P<0.05), there were significant difference among treated groups(P<0.05).4. Apoptosis of rate: Apoptosis of rate of each group is 9.25%, 21.27%, 41.96%, 69.73%, respectively. There were a significant difference among each group(P<0.01). 5. Immunohistochemical results: The expression of Caspase-9 protein in each group was 13.23%, 19.23%, 25.51%, 43.27%, respectively. There was no statistically significant difference among control, paclitaxel,and 125I group(P>0.05). There was statistically significant difference between the combined group and other groups(P<0.05). Caspase-3 were 12.14%,18.45%,27.23%,41.99%,respectively. There was no statistically significant difference among control, paclitaxel,and 125I group(P>0.05). There was statistically significant difference between the combined group and other groups(P <0.05).Conclusions: There was obvious lethal effect after the radioactive iodine-125 combined with paclitaxel in mice. The mechanism of apoptosis may be related to activation of caspase-9 protein,activated caspase -3 protein may induce cell death. |
