The Biological Effect Research Of Interstitial Implanting ¹²⁵ Ⅰ Seed To Treat Prostate Cancer

Prostate cancer（PCA）, a important killer, is threatening the old people’s health, and the incidence of the PCA has obvious local, racial differences. In European and American countries prostate cancer has the highest morbidity among senile male malignant tumors. However, in Asia, especially in China and Japan, southeast Asia, the risk of prostate cancer is low. But along with the arrival of aging society, and the increasingly advanced detection means for prostate cancer, especially blood prostate-specific antigen （PSA） prostate specific antigen, check, transrectal ultrasound guidance, the launch of the prostate biopsy in China greatly improve the prostate cancer detection rate, especially the localized prostate cancer detection rate .According to foreign prostate cancer treatment guidelines and the prostate cancer treatment guidelines formulated in China, prostate cancer treatments, especially localized prostate cancer treatments, basically have radical prostatectomy, outside radi-otherapy and close radiotherapy, etc.The treatment that Brachytherypy on early localized prostate cancer, can achieve reserves and its function, and reduce the complications of radiation, maximum achieve tumor therapy and reduce the damage on normal tissue. The effect of this treatment is better than radical prostatectomy in early stage PCA, although still controversial, but has become a consensus of the international urology and radiotherapy fields. According to the statistics of American radiation oncology, as close radiotherapy has definite effects and significantly less complications than radical surgery, compared with 2000, less than 5% early prostate cancer using radioactive particles implant therapy, the percentage of 2005 rised to 35%, and in the same period of surgical prostate radical resection had fallen to 5% from 35% [3]. But the problem that troubled international urology and radiotherapy fields is: In spite of the positive effects and less side effects, the biological function, characteristics of the treatment are still not very clear. This experiment’s aims are to radioactive particles prostate cancer cell apoptosis induced after exposure of research and nude mouse-animal experiment to investigate the radioactive particles killer prostate cancer with mechanism and the relationship between doses and absorbed dose rate for clinical application, organizational radioactive particles close tumor therapy provides the basis.1 Study on the Mechanisms of prostatic carcinoma tumor cell apoptosis and death induced by different radioactive activity low dose rate irradiation(¹²⁵I)Objective:To found the mechanisms of prostatic carcinoma tumor cell death and diversified dose-rate-effect induced by continuous exceeding different radioactive activity and low does-rate irradiation and curative effect in brachytherapy for prostatic carcinoma, we studied apoptosis and the multiplication of PC3 carcinoma cells in vitro.Methods: The cultured prostate carcinoma cell line PC3 were exposed to different radiation activity from a ¹²⁵I radiation therapy source.（1） To use the inverted microscope to observe the cell。 （2） To study the detection instrument by flow cytometry after different activity illuminate cell apoptosis rate and the cell cycle changes.（3） To study by transmission electron microscope after exposure of cellular.（4） To study the clone formation rate experiment ability change cell proliferation after experimentResults: （1） flow cytometric detection instrument cell apoptosis rate after exposure。With the increasing of radiation activity and time PC3, prostate cancer cell apoptosis rates rise. After each dose radiation 7D group the highest rate higher than some apoptosis each other time. Dose particle activity dose 1.0 MCI, apoptosis rate increased significantly, and reach experimental peak, apoptosis index （AI） for 4.95% + 1.52。（2） To Observe the apoptotic cells form transmission by electron microscopeform 0.4 MCI, 0.6 MCI, 0.8 MCI and 1.0 MCI with blank controls for experimental comparison, observation 48h cells appear typical apoptosis performance, cell volume small, narrow in results shrinks, the nucleus, in nuclear chromatin condensed increased in different blocks and round state, integrating, when chromatin 72h edge this change still exist, and relatively 48h, more typical. To 168h, can be observed in the nucleus, the cells form completely disappear, fractured ¹²⁵I radioactive particles that can cause prostate PC3 cells apoptosis.（3） To detect the cytometric cell cycle by Flow cytometric analysis。Along with the increase of particle doses, G2 / M period cells increased the proportion, S period cells gradually reduce between groups, statistical analysis, are very significant difference （P < 0.01）.4) clone analysis ability changes observed cell proliferationAs particles increases, illuminate radioactive activity prolonged, cells cloned formation rate decreased; Along with the increase of particle activity, the cloning formation rate 3.86% by 55.11% is reduced to the minimum.Conclusion:（1） early inhibiting tumor cell proliferation, is aging, appear tumor cell apoptosis, and become the high apoptosis rate may be ¹²⁵I continued low doses of radiation kill tumor mechanism.（2） ¹²⁵I particles can induce the apoptosis of PC3 prostate cancer,in vitro ,possibly through the cell block in the G2 / M period and cause cell apoptosis.（3） the ability to induce the apoptosis induced by radioactive particles of tumor cell apoptosis is late, from 48h appear hair apoptosis in 168h 48h, scope, with particles - between increased activity of the level increases, appear apoptosis, apoptosis rate increase.2 The experimental research of interstitial implanting ¹²⁵I seed to treat mouse transplanting Prostate cancerObjective: Through the experimental research of the biological effect of implanting ¹²⁵I seed to treat Prostate cancer, in order to get insight of the mechanism of implanting ¹²⁵I seed to kill tumor and to provide academic gist and practice guidance for clinical utilization of ¹²⁵I seed for brachytherapy of Prostate cancerMethods:With statistical principles, bearing nude mice were randomly divided into experimental and control groups （n = 20）, control group and experimental group each further divided into 5 groups （n = 4）. 0.4mci experimental group was implanted with a dose of ¹²⁵I radioactive particles were observed daily after ¹²⁵I seed implantation in nude mice and tumor growth generally. And after implantation 1d, 3d, 5d, 7d, 9d, killed by the corresponding cis experimental group and control group mice, remove the tumor, specimens fixed with 10% formalin and used immunohistochemistry to detect Bax in tumors in vivo expression, in situ end labeling （TUNEL） ¹²⁵I particles detected the extent of apoptosis induced by tumor. During the trial, daily observation of tumor size （a）, the short diameter （b）, calculate the tumor volume （V = ab2 / 2）, body weight （W）, tumor weight of mice were sacrificed （w）, draw tumor growth curve, calculates the population doubling time （T） and the inhibition rate, and analyzed.Results:.（1） ¹²⁵I particle implantation in the treatment of prostate cancer （PC3） The inhibitory rate of the experimental group than the control group.（2） Tunel staining showed: control group, tumor cells grew well, rare cells; the experimental group can be seen early in the apoptotic cells, apoptotic morphology was observed with the radiation time, the apoptotic cells than the control group Increased significantly.（3） 7d after implantation Immunohistochemical control group showed: Bax expression were strongly positive （+++）, positive cells were 71.32±15 .71%; the experimental group was weakly positive expression （+ + +）, positive cells were 8.65±7.25%, the difference was statistically significant （P <0.05）.Conclusion:1. The experiment confirmed for prostate cancer transplantation that ¹²⁵I particles have apparent inhibition melanoma, can cause tissue apoptosis2. This experiment confirmed ¹²⁵I particles inhibited the growth of tumor cell proliferation and induce apoptosis of the tumor. 3. ¹²⁵I particle causes the mechanism of tumor cell apoptosis may be associated with the Bax protein.