^(125)I放射性粒子组织间植入治疗人胰腺癌裸鼠移植瘤的有效性研究

The effectiveness of ^(125)I seed interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice:an experiment in vivo

目的探讨125I放射性粒子组织间植入治疗人胰腺癌裸鼠移植瘤的疗效及其作用机制。方法人胰腺癌SW1990细胞株接种于BABL/c裸鼠右下肢旁腹股沟区偏背侧皮下,成瘤后取瘤块接种,6周后成瘤8～10mm。共16只成瘤大小合适的裸鼠用于实验,分别植入125I粒子(8只)和空载粒子(8只)。粒子植入后,每4天测量肿瘤的长径和短径并称裸鼠体重,裸鼠处死后称量瘤体重。瘤体标本行组织病理学检查、末端脱氧核苷酸转移酶-生物素dUTP切口末端标记法(TUNEL)检测凋亡细胞及免疫组化染色检测增殖细胞核抗原。结果 125I粒子治疗组肿瘤体积增长缓慢,而对照组肿瘤体积增长迅速。实验组和对照组瘤体重分别约(2.68±0.70)g和(4.68±1.45)g,两者的差异有统计学意义(P=0.021);抑瘤率约42.66%。粒子植入前、后实验组和对照组间裸鼠体重对比差异无统计学意义(P>0.05)。治疗组肿瘤细胞坏死明显,而对照组肿瘤细胞无明显或仅有少许坏死。TUENL法检查发现实验组和对照组的凋亡指数分别为(23.2±1.9)%和(8.1±1.5)%,两者的差异有统计学意义(P<0.01)。免疫组化染色发现:实验组及对照组增殖细胞核抗原(PCNA)阳性染色指数分别为(49.8±1.8)%和(82.2±2.4)%,两者的差异有统计学意义(P<0.01)。裸鼠心、肝、肺、肾及脾脏等组织无明显放射性炎症表现。结论 125I粒子组织间植入治疗人胰腺癌裸鼠移植瘤是有效的,其作用机制包括:直接杀伤肿瘤细胞、诱导肿瘤细胞凋亡及降低细胞增殖,并且125I粒子植入瘤体内对周围脏器是安全的。

Objective To discuss the effectiveness and therapeutic mechanism of ^125I interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice.Methods The human pancreatic cell line Sw1990 was subcutaneously injected into the right lower limb partially dorsal area next to the groin of the immunodeficient BABL /c nude mice.The tumor was removed and cut into small pieces after it was formed,then the tumor pieces were inoculated in nude mice.The tumor developed to 8-10 mm in size after six weeks.A total of 16 nude mice with the suitable tumor size were used in this study.The 16 experimental mice were randomly and equally divided into two groups.The mice in study group（n = 8） were implanted with 125I seeds,while the mice in control group（n = 8） were implanted with ghost seeds.After the implantation both the long and short diameter of the tumors as well as the mouse body weight were measured every 4 days.The tumor weight was measured when the mouse was sacrificed.The paraffin-embedded samples were sent for histopathological examination.Apoptotic cells were checked with terminal deoxynucleotidyl transferase dUTP nick end labeling（TUNEL） method.Expression of proliferating cell nuclear antigen（PCNA） was detected with immuno-histochemical staining.Results The tumor grew slowly in the study group,but rapidly in the control group.The tumor weight in the study group and the control group was（2.68 ± 0.70）g and（4.68 ± 1.45）g,respectively,the difference between two groups was statistically significant（P = 0.021）.The tumor inhibition rate was about 42.66%.No significant difference in body weight of nude mice existed between two groups both before and after the treatment（P 0.05）.Marked tumor necrosis was seen in study group,but no obvious,or only a little,tumor necrosis could be observed in the control group.The apoptotic index checked with the TUENL method in the study group and control group was（23.2 ± 1.9）% and（8.1 ± 1.5）%,respectively,and the difference between two groups was statistically significant（P 0.01）.The immunohistochemical staining revealed that PCNA-positive staining index in the study group and control group was（49.8 ± 1.8）% and（82.2 ± 2.4）%,respectively,and the difference was statically significant between two groups（P 0.05）.All the heart,liver,lung,kidney and spleen of the nude mice showed no obvious manifestations of radiological inflammation.Conclusion 125I interstitial brachytherapy is an effective treatment for transplantation tumor of human pancreatic carcinoma in nude mice.Its mechanisms include directly killing the tumor cells,inducing tumor cell apoptosis and reducing cell proliferation.Additionally,125I seeds implantation in vivo tumor is safe for the surrounding organs.