Sava G, Pacor S, Mestroni G, Alessio E
Institute of Pharmacology, School of Pharmacy, University of Trieste, Italy.
Clin Exp Metastasis. 1992 Jul;10(4):273-80. doi: 10.1007/BF00133563.
The antitumor and antimetastatic effects of a ruthenium(III) complex, Na[trans-RuCl4(DMSO)Im], have been examined in mice bearing MCa mammary carcinoma. Na[trans-RuCl4(DMSO)Im] is capable of reducing primary tumor growth and of prolonging the survival time with different schedules of administration. However, better effects were obtained (a) with treatments started soon after tumor implantation, (b) with daily administration rather than with treatments at 4-day intervals and (c) using relatively low daily doses. The prolongation of survival time in tumor-bearing hosts, greater than that obtained with cisplatin, cannot be simply related to the effect on primary tumor growth, always less than that of cisplatin. Rather, emphasis is placed on the reduction of lung metastasis formation, obtained either by i.v. injection of tumor cells (lung colonization or spontaneously from i.m. tumor implants, which is significantly greater than the reduction of primary tumor growth. The antimetastatic effect depends on the treatment schedule and is greater with low doses given daily than with high doses administrated with drug-free intervals. Metastasis reduction involved mainly large metastatic nodules, reducing the average weight of each metastasis by 8-fold for spontaneous metastases and by 5-fold for lung colonies. The antimetastatic action of Na[trans-RuCl4(DMSO)Im] thus indicates the possibility that related analogs can represent a new generation of antitumor compounds capable of selectively interacting with metastasis formation of solid tumors.
已在患有MCa乳腺癌的小鼠中研究了钌(III)配合物Na[trans-RuCl4(DMSO)Im]的抗肿瘤和抗转移作用。Na[trans-RuCl4(DMSO)Im]能够通过不同的给药方案降低原发性肿瘤的生长并延长存活时间。然而,(a)在肿瘤植入后不久开始治疗,(b)每日给药而非间隔4天给药,以及(c)使用相对较低的每日剂量,可获得更好的效果。荷瘤宿主存活时间的延长大于顺铂治疗组,这不能简单地归因于对原发性肿瘤生长的影响,因为其对原发性肿瘤生长的影响始终小于顺铂。相反,重点在于减少肺转移的形成,无论是通过静脉注射肿瘤细胞(肺定植)还是通过肌肉注射肿瘤植入物自发形成的转移,其减少程度均显著大于原发性肿瘤生长的减少程度。抗转移作用取决于治疗方案,每日给予低剂量比间隔给药给予高剂量的抗转移效果更好。转移减少主要涉及大的转移结节,对于自发转移,每个转移灶的平均重量减少8倍,对于肺定植转移,减少5倍。因此,Na[trans-RuCl4(DMSO)Im]的抗转移作用表明,相关类似物有可能代表新一代能够与实体瘤转移形成选择性相互作用的抗肿瘤化合物。