多西他赛与依托泊苷抑制血管肉瘤细胞株ISOS- 1增殖的对比研究(英文)

Inhibitory effect on proliferation of docetaxel vs etoposide on murine angiosarcoma cell line ISOS-1

目的:探讨多西他赛抑制小鼠血管肉瘤细胞株ISOS 1增殖的作用,并与依托泊苷进行比较。方法:体外实验中采用AlamarBlue法检测多西他赛和依托泊苷对体外培养ISOS 1细胞的增殖抑制作用。体内实验中建立小鼠血管肉瘤模型 70只,各实验组与对照组均为 5只,均静脉或腹腔给药。静脉给药法每周 1次, 4次为一个疗程;腹腔给药法每日1次,连续 5次为一个疗程, 2wk后重复 1个疗程。多西他赛和依托泊苷均分为 5, 10, 20mg·kg-1不同剂量组,对照组给予等量生理盐水。观察肿瘤的体积和小鼠生存期。结果:体外实验中,多西他赛对ISOS 1的IC50为 15. 8μg·L-1,明显低于依托泊苷1. 175mg·L-1。体内实验中,静脉法给药时各剂量组,多西他赛比依托泊苷抗肿瘤效果好, 3个剂量组瘤体积抑制率均达 70%以上,多西他赛 5mg·kg-1组与依托泊苷 10mg·kg-1组延长生存期的作用相近。腹腔给药比静脉给药不良反应大, 20mg·kg-1的剂量几乎是致死剂量。结论:多西他赛对于小鼠血管肉瘤细胞株ISOS 1具有较强的增殖抑制作用且优于依托泊苷,低剂量每周 1次静脉给药,是安全有效的,为多西他赛临床应用于血管肉瘤的化疗提供了实验依据。

AIM: To study inhibitory effect on proliferation of docetaxel on murine angiosarcoma cell line (ISOS-1) and compare with etoposide. METHODS: In vitro, the inhibitory effect on proliferation of docetaxel and etoposide on ISOS-1 cells were carried out by Alamar Blue assay. In vivo study, after murine angiosarcoma model establishment, seventy mice were divided into trial and control group with 5 mice for each group. The dosages of docetaxel and etoposide were 5, 10, 20 mg·kg -1 respectively through administration by intravenous (iv) or intraperitoneal (ip) injection. The iv injection was performed once a week and total 4 times as one course. The ip injection was taken once a day, keeping for 5 d as a course and then repeated once more after 2 wk. The control group was injected with the normal saline. The volumes of the tumors and the survival days were calculated. RESULTS: In vitro study, the IC 50 of docetaxel for ISOS-1 cells was 15.8 μg·L -1 showing obviously lower than that of etoposide group(1.175 mg·L -1 ). In vivo study,the anti-tumor effect of docetaxel was better than that of etoposide at three different doses by iv, and all the inhibitory rates of tumor volume were more than 70 %. The life prolonging effect of 5 mg·kg -1 docetaxel was similar to that of etoposide 10 mg·kg -1 . The adverse reactions of ip injection were stronger than those of iv injection. The dosage of etoposide 20 mg·kg -1 almost reached the lethal dose. CONCLUSION: Docetaxel shows obviously inhibitory effects on proliferation of murine angiosarcomacell line (ISOS-1), which is superior to that of etoposide. It is safe and effective with low dosage once a week by iv.