Life prolonging effect of antitumor agents on postoperative adjuvant therapy in the lung spontaneous metastasis model in mice.
Life prolonging effect of antitumor agents on postoperative adjuvant therapy in the lung spontaneous metastasis model in mice.
复制标题
抗肿瘤药物对小鼠肺自发转移模型术后辅助治疗的延长生命作用。
作者：
J. Shibata;K. Murakami;M. Abe;A. Hashimoto;T. Utsugi;M. Fukushima;Yuji Yamada
背景
我们检查了切除原发病灶后给予的各种抗肿瘤药物对肺转移的疗效，原发病灶是通过注射RENCA小鼠肾癌细胞诱导的。
材料和方法
将RENCA细胞植入小鼠的左肾。在植入后第10天进行带有所得原发性肿瘤的左肾的肾切除术，并在第13天开始施用抗肿瘤剂[UFT（20 mg/kg）、5 ′-DFUR（24.6 mg/kg）、5-FU（19 mg/kg）、CDDP（7 mg/kg）、CPT-11（50 mg/kg）、TNP-470（30 mg/kg）]。以抗肿瘤效果和延长生存期为指标评价抗肿瘤药物的疗效。
结果
以肺转移瘤的生长抑制率为指标，UFT组和TNP-470组的抑瘤率分别为55.5%和48.7%。5-FU和CDDP有抑制肿瘤生长的趋势，而5 ′-DFUR和CPT-11无抑瘤作用。UFT和5-FU具有显著的延长生命作用，T/C比值分别为160.8%和125.7%。通过计数肺中转移性结节中的血管数量来检查药物的抗血管生成活性。TNP-470的抑制率为61.5%，其次是UFT、CDDP和CPT-11，抑制率约为30%。对5-FU、SN-38、CDDP和TNP-470的体外细胞毒性进行了检测，发现5-FU具有较强的细胞毒性。
结论
这些结果表明，在该模型中，对肿瘤细胞的细胞毒性和抗血管生成活性是抗肿瘤药物延长生命作用的重要因素，并且可以长期口服的UFT可能在术后辅助治疗中有用。
BACKGROUND
We examined the efficacy against pulmonary metastasis of various antitumor agents administered after excision of the primary lesion, which was induced by injection of RENCA murine renal cancer cells.
MATERIAL AND METHODS
RENCA cells were implanted into the left kidney of the mice. Nephrectomy of the left kidney bearing the resulting primary tumor was performed on day 10 after implantation, and administration of antitumor agents was started on day 13 [UFT (20 mg/kg), 5'-DFUR (24.6 mg/kg), 5-FU (19 mg/kg), CDDP (7 mg/kg), CPT-11 (50 mg/kg), TNP-470 (30 mg/kg)]. The efficacies of antitumor agents were evaluated by antitumor effect and prolongation of life span.
RESULTS
The antitumor effect, which was assayed by growth inhibiting ratio of metastatic tumor in the lung, was significantly in the UFT (55.5%) and TNP-470 (48.7%) treated groups. 5-FU and CDDP exhibited an inhibitory tendency though 5'-DFUR and CPT-11 had no antitumor effect. A significant life-prolonging effect was found for UFT and 5-FU, at a T/C ratio of 160.8% and 125.7%, respectively. The antiangiogenic activity of the agents was examined by counting the number of blood vessels in the metastatic nodules in the lungs. TNP-470 exhibited a strong rate of inhibition of 61.5%, followed by UFT, CDDP and CPT-11, at about 30% inhibition. The in vitro cytotoxicities of 5-FU, SN-38, CDDP and TNP-470 were examined, and 5-FU was observed to have potent cytotoxicity.
CONCLUSIONS
These results suggest that both cytotoxicity to tumor cells and antiangiogenic activity were important factors in the life-prolonging effect of antitumor agents in this model, and that UFT, which can be administered orally long-term, may be useful in postoperative adjuvant therapy.