Matsumoto S, Mashiba H, Okamoto K, Ekimoto H
Anticancer Drugs Dept., Nippon Kayaku Co., Ltd.
Gan To Kagaku Ryoho. 1999 Aug;26(9):1313-20.
The antitumor activity of etoposide (ETP) against human uterine cancer cell lines were investigated in vitro and in vivo. The cytotoxic activity of ETP against HeLa S3, a human cervical cancer cell line, depended on exposure time. The survival rate with 24 h prolonged exposure was reduced to about 1/200 that with 6 h exposure. The time dependency of antitumor activity of ETP against HeLa S3 subcutaneously transplanted in nude mice was studied. The effect of 21 or 28 consecutive days oral administration was greater than that of 5 or 14 consecutive days. Furthermore, a longer administration schedule was less toxic. The antitumor activity of ETP administered orally for 21 consecutive days was compared with that of CDDP, CPT-11 and 5'-DFUR using both human uterine cancer cell lines (TCO-1, SIHA, UCC08JCK) transplanted subcutaneously in nude mice and human uterine cancer cell lines (HeLa S3, UCC08JCK) transplanted into the uterus of nude mice. ETP showed the same antitumor activity as CPT-11 and 5'-DFUR against TCO-1 and UCC08JCK, human uterine cancer cell lines transplanted subcutaneously in nude mice. ETP also showed anticancer activity against two cell lines transplanted into the uterus. The growth inhibition caused by ETP administered orally at 50 mg/kg against HeLa S3 transplanted subcutaneously was 36.7% while that against the same cell line transplanted into the uterus was 58.5%. 5'-DFUR also showed the same antitumor activity as ETP. These results suggest that long term oral administration of ETP is clinically useful for cervical cancer patients.
研究了依托泊苷(ETP)对人子宫癌细胞系的体外和体内抗肿瘤活性。ETP对人宫颈癌细胞系HeLa S3的细胞毒性活性取决于暴露时间。延长暴露24小时后的存活率降至6小时暴露时的约1/200。研究了ETP对裸鼠皮下移植的HeLa S3的抗肿瘤活性的时间依赖性。连续21天或28天口服给药的效果大于连续5天或14天给药的效果。此外,较长的给药方案毒性较小。使用皮下移植到裸鼠体内的人子宫癌细胞系(TCO-1、SIHA、UCC08JCK)和移植到裸鼠子宫内的人子宫癌细胞系(HeLa S3、UCC08JCK),比较了连续21天口服ETP与顺铂、伊立替康和5'-去氧氟尿苷的抗肿瘤活性。ETP对皮下移植到裸鼠体内的人子宫癌细胞系TCO-1和UCC08JCK显示出与伊立替康和5'-去氧氟尿苷相同的抗肿瘤活性。ETP对移植到子宫内的两种细胞系也显示出抗癌活性。50mg/kg口服ETP对皮下移植的HeLa S3的生长抑制率为36.7%,而对移植到子宫内的同一细胞系的生长抑制率为58.5%。5'-去氧氟尿苷也显示出与ETP相同的抗肿瘤活性。这些结果表明,长期口服ETP对宫颈癌患者具有临床应用价值。