中文摘要：

目的：研究鬼臼毒素衍生物YB-1EPN对耐药型S180荷瘤小鼠肉瘤的抑制作用。方法：小鼠一次性腹腔注射700、560、448、358、287mg／kgYB-1EPN，连续观察7d，记录小鼠毒性反应及死亡数，计算半数致死量（LD。）。KM小鼠右腋下移植S180肉瘤以复制S180荷瘤小鼠，采用紫杉醇联合5-氟尿嘧啶及顺铂的治疗方案（简称PFC联合化疗方案）以复制S180荷瘤小鼠耐药模型。抽取耐药型S180荷瘤小鼠腹水接种于KM小鼠腋下以复制耐药型S180小鼠实体瘤。两项小实验均分为空白对照（等容生理盐水，灌胃给药）组、依托泊苷（20．00mg／kg，腹腔给药1次）组与YB-1EPN高、低剂量（11．42、7．14mg／kg，灌胃给药，每天1次，连续7d）组。称小鼠体质量、瘤质量，计算肿瘤抑制率。免疫组化法检测小鼠肿瘤细胞及实体瘤P-糖蛋白（P-gP）的表达。结果：LD。为395．4-485．29mg／kg；与空白对照组比较，YB-1EPN高、低剂量组肿瘤质量减轻，P．gP表达减弱，差异有统计学意义（P〈0．01）。结论：YB-1EPN对耐药型S180小鼠实体瘤有较强的抑制作用。

英文摘要：

OBJECTIVE： To study the antitumor effect of podophyllotoxin derivative YB-1EPN on resistant sarcoma entity in S180 tumor-bearing mice. METHODS： Mice were given disposable intraperitoneal administration of 700, 560, 448, 358.4 and 286.72 mg/kg YB-1EPN for consecutive 7 days. Toxic reaction and the number of dead mice were recorded to calculated LD50. S180 tumor-bearing mice model was induced by resistant S180 sarcoma entity transplanted on right axilla of mice. S180 tumor-bearing mice resistant model was induced by paclitaxel combined with fluorouracil and cisplatin plan （called PFC chemotherapy combina- tion plan）. The ascites of resistant S180 tumor-bearing mice were collected and vaccinated in axilla of mice to estanlish S180 sarco- ma entity. The model mice were divided into blank control group（constant volume of normal saline）, positive control group （etopo- side 20.00 mg/kg, i.p.） and YB-1EPN high-dose and low-dose groups （11.42, 7.14 mg/kg, i.g., once a day for consecutive 7 days）. The body weight and the weight of tumor were weighed, and the inhibitory rate of tumor was calculated. The expression of P-gp in solid tumor was detected by immunohistochemical method. RESULTS： LD-50 was 395.4-485.29 mg/kg; compared with blank control group, the weight of tumor was decreased in YB-1EPN high-dose and medium-dose groups, while the expression of P-gp was attenuated; there was statistical significance （P〈0.01）. CONCLUSIONS： YB-1EPN has a strong inhibitory effect on S180 sarcoma in mice.