Experimental Study On The Treatment Of ～(125)I Seeds Combined With Adriamycin In Nude Mice Bearing Human Breast Cancer

Objective: To assess the mechanism of Iodine-125(I-125) interstitial brachytherapycombined with Adriamycin (ADM) in the treatment of breast cancer and to study itseffects.Methods: 1 In vitro tests, there were four groups: ADM group,¹²⁵I seeds group,¹²⁵Iseeds combined with ADM group and control group. MCF-7 tumor cells were cultured inDMEM (10% NBS) medium with I-125 seeds and/or ADM respectively under 37℃,5%CO₂ air and humidity-controlled condition. ADM, ¹²⁵I seeds, ¹²⁵I seeds combined withADM was added respectively to cell culture bottles, but nothing was done for the controlgroup. In addition, MTT colorimetry was performed too. 2. Animal model establishment ofnude mice bearing human breast cancer. 5×10⁶ MCF-7 tumor cells suspended in 0.1mlDMEM (serum free) were injected into the mammary fat pad (mfp) for each nude mouse.After 2～3 weeks, the mice with tumors about 0.7～1.0cm diameter were selected forexperiment. 3. In vivo tests, total 36 female Nc mice of 4～5 weeks with 20～23g weightwere divided into four groups at random, including ADM group,¹²⁵I seeds group,¹²⁵Iseeds combined with ADM group and control group. Prior to treatment, peripheral bloodleucocytes, mouse weight and tumor size were measured, and then the mice were treatedwith ADM by intraperitoneal injection and/or I-125 seeds implantation into the tumors.I-125 irradiated mice were kept in individual cages with leading. During the treatment,mouse weight, tumor size were measured for three times and peripheral blood leucocyteswere tested for one time. After three weeks' treatment, the mice of all groups were put todeath by dislocation of cervical vertebra, and then seeds were removed. Pathologicexaminations including immunohistochemistry tests and electronic microscope wereperformed with the tumors and some important organs separated from the mice. Data of allgroups were compared with one another by independent-samples T tests. Results: 1. In vitro tests, the results showed that various degrees of cell growthinhibition(GI) were seen in all treatment groups, especially in I-125 seeds combined withADM group. 2. In vivo tests, all mice were alive. The size of tumors was reduced to about0.36cm in I-125 seeds combined with ADM group (P＜0.05, as compared with othergroups); but there were slight changes for peripheral blood leucocytes and also slightchanges for heart, liver and kidney under visual observation. Under pathologicexamination, little tumor cells, obvious fibroses outside, calcifying necroses inside andapoptosis cells were found in the tumor tissue of all treatment groups, especially in I-125seeds combined with ADM group. While in the control group, there were a lot of tumorcells, obvious lymphocytic infiltration, and chest walls' affection in tumor tissue. Withelectron microscope, obvious fibroses around the remnants of the tumor cells, margination,condensation and fragmentation of chromatin in the tumor cell nuclei, swellrough-surfaced endoplasmic reticulum and mitochondria and apoptosis bodies wereobserved in the tumor tissue of all treatment groups; but only slight degeneration of tumorcells was found in the control group. After treatment, the expression of Proliferating CellNuclear Antigen (PCNA) decreased in all groups; Proliferating Index (PI) was(73.39±3.553)%, (46.78±3.579)%, (35.42±3.913)% and (26.09±3.925)% in control group,ADM group, ¹²⁵I seeds group and ¹²⁵I seeds combined with ADM group respectively. Therewas statistic significance of PI in I-125 seeds combined with ADM group (P＜0.01, ascompared with other groups). The expression of Bcl-2 decreased, and Bcl-2 Index wasrespective (20.09±1.694),(12.98±0.951), (11.90±0.748) and (8.97±0.474) in above groups.There was also statistic significance of Bcl-2 Index in I-125 seeds combined with ADMgroup (P＜0.01, as compared with other groups).Conclusion: I-125 seeds emitγ-r's which damage nucleic acid, reticulum andmitochondria of tumor cells, and inhibit their energy metabolism, protein metabolism andnucleic acid metabolism, so cause the apoptosis and death of tumor cells. ADM canoverlap the DNA of tumor cells, inhibit their DNA replication, block their RNApolymerase action and inhibit their RNA synthesis, so cause the apoptosis and death oftumor cells too. Under the combination between I-125 and ADM, it can decrease theexpression of PCNA and Bcl-2, induce apoptosis of MCF-7 tumor cells and inhibit tumorcell proliferation mutually. I-125 interstitial brachytherapy combined with ADM not onlystress full-scale treatment of breast cancer, but also increase its tumor local control rate, so we can achieve the goal of treatment optimization. In a word, I-125 interstitialbrachytherapy combined with ADM can afford a safe, effective and no obvious side effectmethod to treat breast cancer. The treatment influence on the hematopoietic system of nudemice needs further research.