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目的 :观察局部注射趋化因子结合蛋白Du y抗原趋化因子受体(Du y antigen receptor for chemokines,DARC)对肺腺癌A549裸鼠移植瘤生长及肿瘤组织内血管生成的影响。方法:用肺腺癌A549细胞株建立裸鼠移植瘤模型,待肿瘤形成后每3 d1次在瘤体内分别注射不同剂量的DARC蛋白(1、10和100 ng)(低剂量组、中剂量组和高剂量组),同时注射0.9%氯化钠溶液(100μL)作为对照组。观察各组移植瘤的生长情况,以及肿瘤组织中癌栓和微血管密度的情况;采用ELISA法检测移植瘤组织中DARC配体趋化因子C-C基元配体2[chemokine(C-C motif)ligand 2,CCL2]、C-X-C基元配体2[chemokine(C-X-C motif)ligand 2,CXCL2]和CXCL8浓度的改变情况。结果:局部注射DARC蛋白能明显抑制肺癌移植瘤的生长,以高剂量组最为明显;接种后的第39天时高剂量组、中剂量组、低剂量组和对照组移植瘤的体积分别为(95.3±34.2)、(272.4±58.3)、(308.6±132.6)和(670.8±185.7)mm3,与对照组相比各DARC蛋白治疗组小鼠的肿瘤体积均明显缩小(P值均<0.05)。不同剂量的DARC治疗组肿瘤组织中存在癌栓的脉管数和微血管密度均较对照组明显减少;肿瘤组织中CXCL8的浓度明显减少(P值均<0.05),而CCL2和CXCL2的浓度没有明显改变(P值均>0.05)。结论:DARC蛋白通过减少其配体CXCL8浓度来抑制肺癌移植瘤的生长和新生血管的生成。
OBJECTIVE: To observe the effect of local injection of chemokine-binding protein Du y antigen receptor for chemokines (DARC) on the growth of transplanted lung adenocarcinoma A549 xenografts in nude mice and the angiogenesis in tumor tissue. Methods: Nude mice model of lung adenocarcinoma was established by A549 cell line, and different doses of DARC protein (1, 10 and 100 ng) were injected into the tumor every 3 days after tumor formation (low dose group, middle dose group And high dose group), while injecting 0.9% sodium chloride solution (100μL) as the control group. The growth of xenografts in each group and the tumor embolus and microvessel density were observed. The expression of chemokine CC motif ligand 2, CCL2], CXC motif ligand 2, CXCL2], and CXCL8 concentrations. Results: The local injection of DARC protein could significantly inhibit the growth of lung cancer xenografts, especially in the high-dose group. On the 39th day after inoculation, the volume of xenografts in high-dose group, middle-dose group, low-dose group and control group were 95.3 (272.4 ± 58.3), (308.6 ± 132.6) and (670.8 ± 185.7) mm3, respectively. Compared with the control group, the tumor volume of mice in each DARC protein treatment group was significantly reduced (P <0.05). The number of tumor thrombus and microvessel density in the tumor tissues of DARC treatment group were significantly decreased compared with the control group; the concentration of CXCL8 in tumor tissue was significantly decreased (all P <0.05), while the concentration of CCL2 and CXCL2 was not significantly Change (P> 0.05). Conclusion: DARC protein inhibits the growth and angiogenesis of lung cancer xenografts by reducing the concentration of its ligand CXCL8.