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目的研究吉西他滨纳米磁靶向药囊对肺鳞癌A2细胞株体内移植瘤的抑制作用及对癌基因Ras mRNA及Ras蛋白表达的影响。方法选择SPF级雄性裸鼠60只。取处于对数生长期的的肺鳞癌细胞株A2细胞,用含有EDTA的胰酶消化后,悬液接种于在裸鼠右股外侧制作鳞癌移植瘤模型。20 d后选取肿瘤体积约为72.5 mm3的裸鼠作为实验动物模型,并分为5组:(1)Ni Ti合金支气管支架+吉西他滨纳米磁靶向药囊组;(2)Ni Ti合金支气管支架+吉西他滨组;(3)吉西他滨纳米磁靶向药囊组;(4)吉西他滨组;(5)未干预组。Ni Ti合金支气管支架于肿瘤中手术植入,纳米磁靶向药囊或化疗药物通过尾静脉注入,其中吉西他滨纳米磁靶向药囊为本研究自行制备,吉西他滨有效剂量均按45 mg/kg给予。未干预组尾静脉注射同量的生理盐水处理。均连续给药10 d。比较各组处理后的肿瘤生长情况。利用Western Blot和RT-PCR法分别检测治疗后癌组织中Ras蛋白及Ras mRNA的相对表达水平。结果与未干预组相比,Ni Ti合金支气管支架+吉西他滨纳米磁靶向药囊组、Ni Ti支架+吉西他滨组、吉西他滨纳米磁靶向药囊组、吉西他滨组的瘤重和体积均明显减少(P<0.05,P<0.01),其抑瘤率分别为59.0%、38.0%、33.0%、28.0%。Ni Ti合金支气管支架+纳米磁靶向药囊组Ras蛋白、Ras mRNA相对表达水平最低(P均<0.01),与未干预组比较,Ni Ti合金支气管支架+化疗药物组、纳米磁靶向药囊组、化疗药物组Ras蛋白、Ras mRNA相对表达水平均有所下降(P均<0.05),但3组之间差异无统计学意义(P均>0.05)。结论纳米磁靶向药囊合并Ni Ti合金支气管支架可以显著抑制肺鳞癌A2细胞移植瘤的生长,下调癌基因Ras mRNA和Ras蛋白的表达,诱导肿瘤细胞凋亡。
Objective To study the inhibitory effect of gemcitabine nano-magnetic targeted drug-loaded sachets on the transplanted tumor of lung squamous carcinoma cell line A2 in vitro and on the expression of oncogene Ras mRNA and Ras protein. Methods Sixty SPF male nude mice were selected. The lung squamous cell carcinoma cell line A2 in logarithmic growth phase was digested with trypsin containing EDTA and the suspension was inoculated into the squamous carcinoma xenograft model in the right femoral head of nude mice. After 20 days, nude mice with a tumor volume of about 72.5 mm3 were selected as experimental animal models and divided into five groups: (1) Ni Ti alloy bronchial stent + gemcitabine nano-magnetic targeting sachet group; (2) Ni Ti alloy bronchial stent + Gemcitabine group; (3) gemcitabine nano-magnetic targeting sachet group; (4) gemcitabine group; (5) non-intervention group. The Ni Ti alloy bronchial stent was surgically implanted into the tumor, and the nano-magnetic targeting sachet or chemotherapeutic drug was injected through the tail vein. The gemcitabine nano-magnetic targeted sachet was prepared for this study. The effective dose of gemcitabine was given at 45 mg / kg . No intervention group tail vein injection of the same amount of saline treatment. All rats were given continuous administration for 10 days. The growth of tumor in each group was compared. Western Blot and RT-PCR were used to detect the relative expression of Ras protein and Ras mRNA in the treated tissue respectively. Results The tumor weight and volume of Ni Ti alloy bronchial stent + gemcitabine nano-magnetic targeted sachet group, Ni Ti scaffold + gemcitabine group, gemcitabine nano-magnetic target sachet group and gemcitabine group were significantly decreased compared with the untreated group P <0.05, P <0.01). The tumor inhibition rates were 59.0%, 38.0%, 33.0% and 28.0%, respectively. Compared with the non-intervention group, Ni Ti alloy bronchial stent + chemotherapeutic drug group, nano-magnetic targeting drug (P <0.01) The relative expression levels of Ras protein and Ras mRNA in cyst group and chemotherapy group decreased (all P <0.05), but there was no significant difference between the three groups (all P> 0.05). Conclusion Nano-magnetic targeting sachet with Ni Ti alloy bronchial stent can significantly inhibit the growth of lung squamous carcinoma A2 cell xenografts, downregulate the expression of oncogene Ras mRNA and Ras protein, and induce tumor cell apoptosis.