Fan Ying-Fang, Huang Zong-Hai
Department of Surgery, Zhujiang Hospital, The First Military Medical University, Guangzhou 510282, Guangdong Province, China.
World J Gastroenterol. 2002 Oct;8(5):853-6. doi: 10.3748/wjg.v8.i5.853.
To study the effect of angiogenesis inhibitor TNP-470 on peritoneal dissemination of colon cancer in nude mice.
The MTT assay was used to evaluate the inhibitory effect of TNP-470 on human colon cancer cell line Lovo. Lovo cells were injected into the peritoneal cavity of BABL/C nu/nu mice and the models of peritoneal dissemination were developed. Thirty nude mice were randomly divided into control and TNP-470-treated group. In TNP-470-treated group, TNP-470 was injected subcutaneously every other day from day 1 until sacrifice or death (30 mg x kg(-1)). The control group received a sham injection of the same volume saline solution.
In vitro, TNP-470 inhibited the growth of Lovo cells, with its IC50 at 2.14 X 10(2) microg x L(-1). In vitro, TNP-470 demonstrated growth inhibition of tumors. Mice body weight and abdominal circumferences were significantly different between TNP-470-treated group (24.5+/-3.2 g, 7.0+/-1.1 cm) and control group (29.5+/-2.1 g, 10.3+/-1.5 cm), P=0.005 and P=0.001. The number of disseminated foci was significantly different between the control group (92.1+/-20.6) and the TNP-470-treated group (40.3+/-12.3), P<0.001. The maximal size of foci was significantly smaller in TNP-470-treated group (3.3+/-0.7 mm) than that of control (7.3+/-2.3 mm), P=0.004. Mean survival time was significantly longer in TNP-470-treated group(98.00+/-12.06 d) than that in control group (41.86+/-9.51 d), P<0.001.
Angiogenesis inhibitor TNP-470 might be effective in treating peritoneal dissemination of colon cancer and improve the survival rate of nude mice.
研究血管生成抑制剂TNP - 470对裸鼠结肠癌腹膜播散的影响。
采用MTT法评估TNP - 470对人结肠癌Lovo细胞系的抑制作用。将Lovo细胞注入BABL/C nu/nu小鼠腹腔,建立腹膜播散模型。30只裸鼠随机分为对照组和TNP - 470治疗组。在TNP - 470治疗组,从第1天开始每隔一天皮下注射TNP - 470,直至处死或死亡(30 mg·kg⁻¹)。对照组注射相同体积的生理盐水作为假注射。
体外实验中,TNP - 470抑制Lovo细胞生长,其IC50为2.14×10² μg·L⁻¹。体内实验中,TNP - 470显示出对肿瘤生长的抑制作用。TNP - 470治疗组(24.5±3.2 g,7.0±1.1 cm)与对照组(29.5±2.1 g,10.3±1.5 cm)的小鼠体重和腹围存在显著差异,P = 0.005和P = 0.001。对照组(92.1±20.6)与TNP - 470治疗组(40.3±12.3)的播散病灶数量存在显著差异,P<0.001。TNP - 470治疗组病灶的最大尺寸(3.3±0.7 mm)显著小于对照组(7.3±2.3 mm),P = 0.004。TNP - 470治疗组的平均生存时间(98.00±12.06 d)显著长于对照组(41.86±9.51 d),P<0.001。
血管生成抑制剂TNP - 470可能对治疗结肠癌腹膜播散有效,并提高裸鼠的生存率。