| Objective:To investigate the interstitial implantation of Combined125I seed brachytherapy with interstitial chemotherapy to treat mice metastatic tumors and its mechanism of the H22cell proliferationMethods:8×106/0.2ml H22hepatoma carcinoma cells were transplanetd subcutaneously in the right armpit of40KM-mices to established transplanted sarcoma. After7days,Subcutaneous sarcoma can be touch by hand, which size is1cm×1cm.Tumor-bearing mice randomly divided into4groups (10cases each group).125I seed((surface radioactivity33.45MBq) and5-FU embedded into each tumor in group A,125I seed in group B,5-FU in group C, and dummy seeds in the group D. The survival rates of mice and the tumor size were measured in each4days. After28days, the tumor-bearing mice were executed,pathology and electron microscopy examination was measured. And the gene expression of bcl-2and bax was examined by immunohistochemical method and RT-PCR.Results:Part1:4days after the interstitial implantation of125I seed, there were no volume difference the control group tumor and treatment groups tumor.After12days,the proliferation in treatment mice is much fast than the control group.28days larer the average xenograft volume in the group A was (1.38±0.11)cm3,in the group B was (2.11±0.19) cm3,in the group C was(2.79±0.23) cm3,in the group D was (4.34±0.29) cm3.There was significant difference bewteen the4groups xenograft volumes (P<0.05).The tumor volume inhibition rate of the treatment groups were87.28%,74.33%and58.59%.Pathological results showed,in the125I seed brachytherapy groups varying degrees of tumor cell structure was destroyed, the cell structure was disappeared, there were coagulation necrosis in large area,and extensive fibrosis around the tumor,the small blood vessels were dilatation and congestion, and lymphocytic infiltration.In the control group, there were minor fibrosis surrounding blank seeds,tumor cells were full vision,but the tissue necrosis was less.At the electron microscope showed,the treatment groups had different levels of tumor cell apoptosis,there were multiple cytoplasmic processes,nuclear condensation, lysed, and chromatin was also dense.In the combined treatment group, there was seen a large number of dark cells and apoptotic bodies were swallowed,but full vision of tumor cells in the control group.Part2:Immunohistochemistry analysis and RT-PCR had showed that the expression of Bcl-2gene and the ratio of Bcl-2/Bax in all treatment groups were lower than that in the control group, but the expression of Bax gene in all treatment groups were higher than that in the control group. In treatment groups, the Group As expression of Bcl-2gene and the ratio of Bcl-2/Bax were lower than the other group,the expression of Bax gene was higher than the others. Differences between the treatment groups and the control group was statistically significant (P<0.05),so as the difference among treatment groups(P<0.05).Conclusion:Interstitial implantation of125I seed can be lowered the expression of Bcl-2gene and raise of the expression of Bax gene to promote apoptosis of H22hepatoma cells125I seed combined with interstitial chemotherapy can be lowered further, Bcl-2/Bax ratio, which further inhibit cancer cell growth, and promote the cell's degeneration,necrosis and apoptosis of hepatocellular carcinoma tumor cells. Combination of two treatment have synergistic effect, will reduce the dose of chemotherapy or costs, and reduce systemic cytotoxic response. Further improve the lack of125I seed dose of "cold spots", provides a simple and effective new treatment for the clinical treatment, for which reason can not be the ideal distribution125I seed in liver cancer. |
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