TNP--470对结肠癌裸鼠腹水瘤生长的抑制作用

Inhibitory effect of TNP-470 on colon cancer in nude mice

目的:研究血管生成抑制剂TNP-470对裸鼠荷人结肠癌腹水瘤生长的抑制作用。方法:采用MTT法检测TNP-470对结肠癌LOVO细胞的生长抑制作用。将LOVO细胞注入Balb/c裸鼠腹腔,建立结肠癌腹水瘤模型。30只裸鼠随机分成TNP-470组(30mg/kg,sc, qod)和对照组(给相同体积生理盐水)。结果:TNP-470可抑制LOVO细胞的体外生长,IC50为2.14×10~2μg·L^(-1)。两组裸鼠体质量分别为24.5±3.2g,29.5±2.1g;腹围分别为7.0±1.1cm, 10.3±1.5cm;腹腔肿瘤结节数分别为40.3±12.3个,92.1±20.6个;腹腔最大结节直径分别为3.3±0.7mm,7.3±2.3mm。统计分析表明:在鼠重、腹围、腹腔转移结节数、腹腔最大结节直径等方面,TNP-470组与对照组比较均有显著性差异(P=0.005,P=0.001,P<0.001,P=0.004)。在累积生存率方面:治疗组和对照组的中位生存期分别为92d和40d,两组裸鼠生存时间也有显著差异(P<0.001)。结论:TNP-470能有效地抑制结肠癌腹水形成和腹腔播散结节生长,提高荷瘤裸鼠的生存率。

AIM: To study the effect of angiogenesis inhibitor TNP-470 on colon cancer in nude mice. METHODS: The MTT assay was used to evaluate the inhibitory effect of TNP-470 on human colon cancer cell line, LOVO cells. LOVO cells were injected into the peritoneal cavity of Balb/c nu/nu mice and the models of peritoneal dissemination were developed. Thirty nude mice were randomly divided into a control and a TNP-470-treated group. In TNP-470-treated group, TNP-470 was injected subcutaneously every other day from day luntil sacrifice (30mg/kg). The control group received a sham injection of the same volume saline solution. RESULTS: In vitro, TNP-470 inhibited the growth of LOVO cells, with its IC50 at 2.14×10~2μg·L^(-1). In vivo, TNP-470 demonstrated growth inhibition of tumors. The number of disseminated loci had a significant difference between TNP-470-treated group (40.3±12.3) and control group (92.1±20.6) (P<0.001). The maximum size of foci was significantly smaller in TNP-470-treated group (3.3±0.7mm) than that of control (7.3±2.3mm) (P=0.004). Mice body weight and abdomen circumference had significances different between TNP-470-treated group (24.54±3.2g, 7.0±1.1cm) and control group (29.5±2.1g, 10.3±1.5cm)(P=0.005 and P=0.001). Survival time was significantly longer in TNP-470-treated group than that of contro (P<0.001). CONCLUSIONS: Angiogenesis inhibitor TNP-470 is effective in treating ascites growth and peritoneal dissemination of colon cancer and improves the survival rate of nude mice with the cancer.