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亲嗜细胞性异质分子脂质(CHML)对裸鼠人乳腺癌异种移植瘤的抗肿瘤活性。

Antitumor activity of cytotropic heterogeneous molecular lipids (CHML) on human breast cancer xenograft in nude mice.

作者信息

Zhan Q, Zhao S C, Xu Z

机构信息

Department of Radiation Oncology, Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213, USA.

出版信息

Anticancer Res. 2001 Jul-Aug;21(4A):2477-82.

Abstract

Cytotropic heterogeneous molecular lipid (CHML), which is a new anticancer agent with US patent number 5,260,067, has recently been shown to suppress tumor cell growth in multiple tumor lines and induce apoptosis in vitro (1). These results indicate that CHML may be an effective antitumor agent. In the present study, using both local injection and intravenous injection, we have investigated the suppressive effect of CHML on human breast caner cells MCF-7 xenograft in nude mice. In the local injection, CHML was introduced into nude mice implanted with human breast cancer xenograft at doses of 25 mg/tumor area (cm2), 35 mg/tumor area (cm2), or 50 mg/tumor area (cm2), once every two days, total 3 times. The inhibition of tumor growth was 81.3%, 93.8% and 100%, respectively. In the intravenous injection, the nude mice bearing MCF-7 xenografts were treated with CHML at 10 mg/kg/day, or 15 mg/kg/day, or 20 mg/kg/day, once a day, total 7 days, the growth inhibition of tumor area was 58.1%, 77.4%, and 83.9%, respectively. At the same time, the toxicity of CHML was determined through examining the number of the white blood cell (WBC) and the activity of the serum glutamic-pyruvic transaminase (SGPT). However, no evident alterations of WBC and SGPT were detected in all animals treated with CHML, suggesting that CHML has little toxicity on nude mice. Taken together, these results indicate that CHML is an effective agent that suppresses breast tumor growth and suggest the possibility of using CHML in the clinical trial in the near future.

摘要

亲嗜性异质分子脂质(CHML)是一种拥有美国专利号5,260,067的新型抗癌药物,最近研究表明其能抑制多种肿瘤细胞系的生长,并在体外诱导细胞凋亡(1)。这些结果表明CHML可能是一种有效的抗肿瘤药物。在本研究中,我们通过局部注射和静脉注射两种方式,研究了CHML对裸鼠人乳腺癌细胞MCF-7异种移植瘤的抑制作用。在局部注射中,将CHML以25mg/肿瘤面积(cm²)、35mg/肿瘤面积(cm²)或50mg/肿瘤面积(cm²)的剂量,每两天注射一次,共注射3次,引入接种了人乳腺癌异种移植瘤的裸鼠体内。肿瘤生长抑制率分别为81.3%、93.8%和100%。在静脉注射中,对携带MCF-7异种移植瘤的裸鼠,分别以10mg/kg/天、15mg/kg/天或20mg/kg/天的剂量,每天注射一次,共注射7天,肿瘤面积的生长抑制率分别为58.1%、77.4%和83.9%。同时,通过检测白细胞(WBC)数量和血清谷丙转氨酶(SGPT)活性来确定CHML的毒性。然而,在所有接受CHML治疗的动物中,未检测到WBC和SGPT有明显变化,这表明CHML对裸鼠毒性很小。综上所述,这些结果表明CHML是一种抑制乳腺肿瘤生长的有效药物,并提示在不久的将来有可能将CHML用于临床试验。

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