持续小剂量化疗对A549肺癌生长及VE-Cadherin的影响

Effect of Low-dose Metronomic Chemotherapy on Growth Rate and VE-Cadherin of A549 Pulmonary Adenocarcinoma in Athymic Mice

目的检测不同剂量环磷酰胺化疗后,荷A549肺腺癌裸鼠皮下肿瘤生长情况及肿瘤组织中VE-Cadherin的表达。方法右季肋部皮下注射A549细胞悬液,建立荷A549肺腺癌裸鼠模型,分为三组,分别给予持续小剂量(Low-Dose Metronomic,LDM)CTX(环磷酰胺)、最大耐受剂量(MaximumTolerable Dose,MTD)CTX和0.9%氯化钠溶液化疗,每周测量肿瘤体积,21天治疗结束取皮下肿瘤组织,以免疫组织化学SP法检测三组裸鼠皮下肿瘤组织中VE-Cadherin的表达,以RT-PCR法检测癌组织中VE-Cadherin基因含量。结果持续小剂量组肿瘤生长明显慢于大剂量组和对照组,VE-Cadherin表达及基因含量显著低于大剂量组和对照组(P<0.05)。结论持续小剂量化疗可以使癌组织中VE-Cadherin表达下调,抑制肿瘤血管生成,从而持续抑制肿瘤生长。

Objective To investigate the growth rate and the expression of VE-Cadherin of tumor graft of the human pulmonary adenocarcinoma in nude mouse after chemotherapy with different dose of CTX.Methods Eighteen nude mice were subcutanously injected under the anterior right leg with cultured A549 cell suspend fluid.All the nude mice were devided into 3 groups.They were separately accepted the treatment of LDM CTX,MTD CTX and 0.9%NS.The volume of tumors were measured every week by sliding caliper.All nude mice were killed on the 21th day after treatment,then the tumors were taken out.Immunohistochemistry（Strepatacidin peroxidase System for Immunohistological Staining）was used to detect the expressions of VE-Cadherin and RT-PCR was used to detect the content of VE-Cadherin gene in the tumor tissues from 18 cases of nude mice.Results The growth rate,expressions of VE-Cadherin and content of VE-Cadherin gene in LDM group were significantly lower than that either in MTD group or in control group（P0.05）.Conclusion The Low-Dose Metronomic chemotherapy can down-regulate the level of VE-Cadherin and suppress the angiogenesis of tumor consequently then suppress the growth of tumor.