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目的探讨5-氮杂-2’-脱氧胞苷(5-Aza)联合临床化疗药物紫杉醇与氟尿嘧啶对于胃癌裸鼠移植瘤生长的抑制作用和抑癌基因RUNX3 mRNA以及肿瘤转移相关蛋白E-cadherin与Vimentin表达的影响。方法建立胃癌细胞株MKN-45的裸鼠移植瘤模型,分为0.9%氯化钠注射溶液对照、5-Aza(2 mg/kg,每天1次)、化疗药物(1 mg/kg紫杉醇与5 mg/kg氟尿嘧啶,分别于治疗周期第1、8天用)以及5-Aza与紫杉醇及氟尿嘧啶联合用药,采用腹腔注射方法给药3周。观察各组裸鼠移植瘤的生长速度变化,并用RT-PCR方法检测肿瘤RUNX3基因的mRNA表达水平,免疫组织化学方法检测E-cadherin与Vimentin表达情况。结果胃癌细胞MKN-45裸鼠移植瘤模型经药物治疗3周后,与空白对照组相比,5-Aza组或T+F组的移植瘤生长速度明显减慢(P<0.05),而且5-Aza与T+F联合治疗组比单独处理组的肿瘤生长速度下降更为显著(P<0.05)。通过作用机制分析发现,与对照组相比,化疗药物T+F组RUNX3 mRNA及E-cadherin与Vimentin蛋白表达水平无明显变化;5-Aza处理组RUNX3 mRNA与E-cadherin蛋白表达水平有明显升高,Vimentin表达水平有明显下降;药物联合组RUNX3 mRNA与E-cadherin蛋白表达水平升高明显,而Vimentin表达水平下降更为显著。结论 5-Aza具有抑制胃癌裸鼠移植瘤生长与转移的能力,联合化疗药物紫杉醇与氟尿嘧啶处理效果更显著。5-Aza发挥肿瘤抑制功能可能是通过提高抑癌基因RUNX3基因表达实现的。
Objective To investigate the inhibitory effects of 5-Aza-5-Aza combined with 5-Aza and 5-Fluorouracil on the growth of gastric cancer xenografts in nude mice and the expression of RUNX3 mRNA and tumor metastasis-associated protein E-cadherin The impact of Vimentin expression. Methods The nude mice model of gastric cancer cell line MKN-45 was established and divided into 0.9% sodium chloride injection solution, 5-Aza (2 mg / kg once daily), chemotherapy with paclitaxel mg / kg fluorouracil, respectively, on days 1 and 8 of the treatment cycle) and 5-Aza in combination with paclitaxel and fluorouracil for 3 weeks by intraperitoneal injection. The growth of xenografts in nude mice in each group was observed. The mRNA expression of RUNX3 was detected by RT-PCR and the expression of E-cadherin and Vimentin was detected by immunohistochemistry. Results The growth of transplanted tumor in 5-Aza group or T + F group was significantly slower than that of the blank control group (P <0.05) after 3 weeks of drug treatment in the gastric cancer MKN-45 xenografted model in nude mice. The combination of -Aza and T + F decreased the tumor growth rate more significantly than the group treated alone (P <0.05). Through the mechanism of action analysis, compared with the control group, the expression of RUNX3 mRNA and E-cadherin and Vimentin protein in T + F group did not change significantly; the expression of RUNX3 mRNA and E-cadherin protein in 5-Aza group was significantly increased High, Vimentin expression levels decreased significantly; drug combination group RUNX3 mRNA and E-cadherin protein expression increased significantly, while the Vimentin expression level decreased more significantly. Conclusions 5-Aza has the ability of inhibiting the growth and metastasis of gastric cancer xenografts in nude mice, and the combination chemotherapy of paclitaxel and fluorouracil is more effective. 5-Aza tumor suppressor function may be by increasing the tumor suppressor gene RUNX3 gene expression.