Schirner M, Schneider M R
Research Laboratories, Experimental Oncology, Schering AG, Berlin, Germany.
Int J Cancer. 1995 Jul 17;62(2):205-9. doi: 10.1002/ijc.2910620216.
Cicaprost, a stable prostacyclin analogue, has been shown to be anti-metastatically active in a series of metastasizing rodent tumors. Start of treatment with cicaprost immediately before tumor implantation was a characteristic feature of our previous investigations. We have reported that in rats bearing mammary-fat-pad-implanted SMT2A mammary carcinoma, cicaprost treatment starting before tumor implantation led to a strong decrease in the number of lung metastases. In order to determine the effect on occult tumor metastasis, the present study examined the effect of starting treatment when tumor metastasis is already present. Cicaprost in daily oral doses of 0.1 mg/kg given from day 10 to day 32 reduced the number of lung metastases by about 75% compared with the control, whereas surgical removal of palpable primary tumors on day 5 or day 10 failed to influence lung metastasis. Using different treatment schedules, a pronounced reduction of the number of lung metastases was achieved by administration of cicaprost until the end of the experiment (from day 5 to day 35), whereas short-term treatments (from day 5 to day 15 or to day 25) were without significant effect. In rats whose SMT2A tumors were surgically removed 10 days after tumor implantation, there was a strong decrease of lung metastases by cicaprost given from day 20 to day 36. In addition to its inhibitory potential in animals with advanced tumor disease, cicaprost showed anti-metastatic action when used in peri-operative treatment of animals whose primary tumors had been removed. In conclusion, the present results demonstrate that cicaprost exhibits strong anti-metastatic activity in the SMT2A rat mammary-carcinoma model with treatment started when occult tumor metastases are already present. Results also indicate that direct effects on tumor cells may contribute to the anti-metastatic action of cicaprost in spontaneously metastasizing tumors.
西卡前列素是一种稳定的前列环素类似物，已被证明在一系列转移性啮齿动物肿瘤中具有抗转移活性。在肿瘤植入前立即开始用西卡前列素治疗是我们先前研究的一个特征。我们曾报道，在植入乳腺脂肪垫的SMT2A乳腺癌大鼠中，在肿瘤植入前开始西卡前列素治疗可导致肺转移数量大幅减少。为了确定对隐匿性肿瘤转移的影响，本研究考察了在肿瘤转移已经存在时开始治疗的效果。从第10天至第32天每天口服0.1mg/kg的西卡前列素，与对照组相比，肺转移数量减少了约75%，而在第5天或第10天手术切除可触及的原发性肿瘤未能影响肺转移。采用不同的治疗方案，在实验结束前（从第5天至第35天）给予西卡前列素可显著减少肺转移数量，而短期治疗（从第5天至第15天或至第25天）则无显著效果。在肿瘤植入10天后手术切除SMT2A肿瘤的大鼠中，从第20天至第36天给予西卡前列素可使肺转移显著减少。除了在晚期肿瘤疾病动物中具有抑制潜力外，西卡前列素在原发性肿瘤已被切除的动物围手术期治疗中也显示出抗转移作用。总之，目前的结果表明，在隐匿性肿瘤转移已经存在时开始治疗，西卡前列素在SMT2A大鼠乳腺癌模型中表现出强大的抗转移活性。结果还表明，对肿瘤细胞的直接作用可能有助于西卡前列素在自发转移肿瘤中的抗转移作用。
