^99Tc-亚甲基二膦酸盐与^153Sm-乙二胺四亚甲基膦酸对骨侵袭和骨质溶解抑制作用的对比研究

The comparative study of inhibitory effects of ^99Tc-methylenediphosphonate and ^153Sm-ethylene diamine tetramethylene phosphonic acid on bone invasion and osteolysis

目的对比观察^99Tc-亚甲基二膦酸盐（^99Tc-MDP）与^153Sm-乙二胺四亚甲基膦酸（^153Sm-EDTMP）对Walker256癌细胞引起的大鼠骨侵袭和骨质溶解的抑制作用及二者对移植瘤细胞的影响。方法建立Walker256癌大鼠骨侵袭和骨质溶解模型。设空白对照组、^99Tc-MDP治疗组、153Sm—EDTMP治疗组、^99Tc-MDP＋^153Sm-EDTMP治疗组，采用^99Tc^m--MDP全身骨显像、骨骼x线片及胫骨病理切片方法观察两种药物单独或联合应用对荷瘤大鼠骨侵袭和骨质溶解的抑制作用，并通过流式细胞仪分析两种药物对移植瘤细胞的影响。结果与对照组相比，^99Tc-MDP治疗组、^153Sm-EDTMP治疗组、^99Tc-MDP＋^153Sm-EDTMP治疗组均能明显抑制荷瘤大鼠骨侵袭和骨质溶解（确切概率法：P〈0．05）。两种药物联合应用与单独应用相比未见明显差异。各治疗组移植瘤细胞的凋亡率明显高于对照组，S期的细胞比例明显下降，二者联合应用的作用更明显。结论①^99Tc-MDP及^153Sm-EDTMP对荷Walker256癌大鼠均有抑制骨侵袭和骨质溶解的作用；②两种药物在诱导移植瘤细胞凋亡、抑制移植瘤细胞增殖方面均有一定作用，二者联合应用的作用更明显。

Objective To observe the inhibitory effects of ^99Tc-methylenediphosphonate （^99Tc-MDP） and ^153Sm-ethylene diamine tetramethylene phosphonic acid （^153Sm-EDTMP） on bone invasion and osteolysis by Walker 256 carcinoma in rats, and their influence on the implanted tumor cells comparatively. Methods Bone invasion and osteolysis model was induced by Walker 256 carcinoma cells. The animals were divided into four groups： control group, ^99Tc-MDP treatment group, ^153Sm-EDTMP treatment group and ^99Tc-MDP＋ ^153Sm-EDTMP treatment group. Radionuclide bone scan of ^99Tc^m-MDP, X-ray and histological examination were used in the experiment to estimate the inhibitory effects of ^99Tc-MDP or/and ^153Sm-EDTMP on the bone invasion and osteolysis. Meanwhile, the rate of apoptosis and percentage of each cell cycle phase of the ratimplanted tumor were analyzed by flow cytometry. Results Compared with the control, the rat number of tibia invasion and bone absorption reduced markedly in ^99Tc-MDP treatment group, ^153Sm-EDTMP treatment group and ^99Tc-MDP＋^153Sm-EDTMP treatment group（Fisher＇ s exact test： P〈0.05）. The rat number of bone absorption in the ^99Tc-MDp＋153Sm-EDTMP treatment group was lower than that of ^99Tc-MDP treatment group and ^153Sm-EDTMP treatment group. However, there was no significant difference. In addition, the rate of cell apoptosis in all the treatment groups was greater than that of the control group. And the cell percentage of DNA synthesis phase（S phase） notably dropped. There was enhancive effect on the transplanted tumor cells when both ^99Tc-MDP and ^153Sm-EDTMP were injected into the Walker 256 bearing rats. Conclusions （1）^99Tc-MDP and ^153Sm-EDTMP can obviously prevent bone invasion and osteolysis induced by Walker 256 carcinoma in rats. （2）They also have an effect on inducing the apoptosis of implanted tumor cells and inhibiting the proliferation of the transplanted tumor ceils. There is enhancive effect on the implanted tumor cells when ^99Tc-MDP and ^153Sm-EDTMP are applied simultaneously.