Therapeutic effect and distribution of (32)P-chromic-poly (L-lactide) brachytherapy in nude mice bearing human prostate cancer

Abstract

Objective To investigate the anti-tumor effects and distribution of 32P-chromic-phosphate poly(L-lactide)(CP-PLLA) in nude mice bearing the prostate cancer cell line PC-3M.Methods Tumor xenograft models were established with PC-3M prostate cancer cell line in male BALB/c nude mice.Based on the implanted dosage of 32P-CP-PLLA particles,the mice were randomly divided into four groups:control group (n =8,0 MBq),low-dose group (n =8,3.7 MBq),middle-dose group (n =8,7.4 MBq) and high-dose group (n =8,18.5 MBq).Three mice from each group were sacrificed 2 d after the 32P-CPPLLA particles were implanted into the tumor.Cell apoptosis was analyzed by a terminal oxynucleotidyl transferase mediated dUTP biotin nick and labeling (TUNEL) method,upon which the apoptotic rate was calculated.Tumor volume was measured every two days.The in vivo distribution of 32P-CP-PLLA was observed by SPECT.Mice in each group (n =5) were sacrificed on the 14th day.The weight and radioactivity of tumors were measured,so that the radioactive retention ratio and tumor growth inhibition rate could be calculated.The pathological changes of tumors and livers were observed,allowing the tumor necrotic rate to be calculated.The intratumoral microvessel density (MVD) was evaluated by an immunohistochemical method.Statistical analysis was performed by one-way analysis of variance and SNK-q analysis.Results 32P mainly accumulated in the tumor.Significant differences were noted in the tumor volumes among all groups on the 14th day (F =212.820,P ＜ 0.01).Massive tumor necrosis was observed by pathologic examination.After exposure to 0,3.7,7.4 and 18.5 MBq 32P-CP-PLLA,the apoptotic rates of tumors on the 2nd day were (1.66 ±0.56)％,(34.51 ±6.68)％,(42.45 ±6.09)％ and (57.01 ±3.13)％,respectively.On the 14th day,the tumor necrotic rates were (4.86 ±4.12)％,(65.43 ±8.06)％,(76.18 ±6.35)％ and (85.85 ±3.05)％,respectively and the tumor growth inhibition rates were (60.82 ± 3.81) ％,(73.17 ± 4.55) ％,(8 1.80 ± 4.74) ％,respectively.The apoptotic rate,tumor necrotic rate and tumor growth inhibition rate all showed a dose-effect relationship.When the dose was 3.7,7.4 and 18.5 MBq,the radioactive retention ratios in the tumors were (34.36 ±5.78)％,(41.16 ±5.26) ％ and (44.70 ± 3.83) ％,respectively (F =6.311,P ＜ 0.05).When the dose was 0,3.7,7.4 and 18.5 MBq,the MVD was 62.00 ±5.40,38.16 ±4.16,23.50 ±4.59 and 15.80 ±3.92,respectively (F=128.613,q=14.31,23.11,27.74,8.80,13.43,4.62,all P＜0.01).No pathological changes were observed in the liver or spleen.Conclusions The 32P-CP-PLLA particles released in the tumor and accumulated significantly at the implantation site.It shows apparent antitumor effects,including inducing apoptosis and inhibiting angiogenesis.In addition,a dose-effect relationship is noted between the antitumor effects and radioactive retention ratios of the tumors. Key words: Prostatic neoplasms; Neoplasm transplantation; Brachytherapy; Phosphorus radioisotopes; Chromic phosphate-poly (L-lactide); Mice, nude