论文部分内容阅读
目的比较去甲斑蝥素(NCTD)最大耐受剂量化疗(MTD)和低剂量节拍式化疗(LDM)对荷人源肝癌裸鼠肿瘤的生长抑制作用,评价其不良反应,并探讨不同给药方案对血管内皮生长因子(VEGF)蛋白和CD44蛋白表达水平的影响。方法采用人肝癌细胞株建立荷人肝癌裸鼠皮下移植瘤模型。将裸鼠随机分为3组:对照组、NCTD-MTD组、NCTD-LDM组。给药期间测量裸鼠肿瘤体积大小,并观察裸鼠生存情况。处死后计算抑瘤率并检测血清中丙氨酸氨基转移酶(ALT)和肌酐浓度。免疫组化法检测移植瘤组织中VEGF和CD44蛋白表达水平。结果从给药后第9天开始,NCTD-LDM组对肿瘤体积增长的抑制作用明显优于其他2组(P<0.05);给药结束后,对照组、NCTD-MTD组和NCTD-LDM组的瘤质量分别为(0.78±0.22)、(0.73±0.21)和(0.48±0.20)g,NCTD-MTD组和NCTD-LDM组的肿瘤抑制率分别为5.58%和42.83%,NCTD-LDM组相对其他2组的瘤质量差异有统计学意义(P<0.05)。免疫组化结果显示,NCTD-LDM组的VEGF蛋白和CD44蛋白的表达明显低于其他2组;生化结果显示,NCTD-MTD组裸鼠的ALT值和血清肌酐值明显高于对照组和NCTD-LDM组(P<0.05),而NCTD-LDM组并未见明显升高。结论在总给药剂量相同的情况下,NCTD-LDM化疗可显示出更优的肿瘤抑制效果,并对肝肾功能的影响较小,其抗肿瘤机制可能是通过对肿瘤血管和肿瘤细胞转移的抑制作用来提高化疗效果。因此,LDM化疗有望成为提高抗肿瘤效果和降低不良反应的一种理想模式。
Objective To compare the inhibitory effects of norcantharidin (MTT) and low-dose metronomic chemotherapy (LDM) on tumor growth in human hepatoma-bearing nude mice and to evaluate its adverse reactions and to explore different dosage regimens On vascular endothelial growth factor (VEGF) protein and CD44 protein expression levels. Methods Human hepatocellular carcinoma cell lines were used to establish the model of subcutaneous xenografts in nude mice bearing human hepatocellular carcinoma. The nude mice were randomly divided into 3 groups: control group, NCTD-MTD group, NCTD-LDM group. The tumor volume of nude mice was measured during the administration, and the survival of nude mice was observed. After sacrifice, the tumor inhibition rate was calculated and serum alanine aminotransferase (ALT) and creatinine concentrations were measured. Immunohistochemistry was used to detect the expression of VEGF and CD44 in the tumor tissue. Results The NCTD-LDM group was significantly better than the other two groups on the 9th day after administration (P <0.05). After the administration, NCTD-LDM group and NCTD-LDM group (0.78 ± 0.22), (0.73 ± 0.21) and (0.48 ± 0.20) g, respectively. The tumor inhibition rates in NCTD-MTD group and NCTD-LDM group were 5.58% and 42.83% The other two groups of tumor mass difference was statistically significant (P <0.05). Immunohistochemical results showed that NCTD-LDM group VEGF protein and CD44 protein expression was significantly lower than the other two groups; biochemical results showed that NCTD-MTD nude mice ALT value and serum creatinine values were significantly higher than the control group and NCTD- LDM group (P <0.05), but no significant increase in NCTD-LDM group. Conclusions NCTD-LDM chemotherapy can show better tumor inhibition effect and less effect on liver and kidney function under the same total dose of chemotherapy. The anti-tumor mechanism may be through the metastasis of tumor blood vessels and tumor cells Inhibition to improve the effect of chemotherapy. Therefore, LDM chemotherapy is expected to become an ideal model to improve anti-tumor effect and reduce adverse reactions.