趋化因子IP10抑制乳腺癌细胞4T1播散转移的研究

来源 :中华医学杂志 | 被引量 : 0次 | 上传用户:scarllie
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目的观察增强IP10在肿瘤局部的表达对乳腺癌细胞4T1远端播散转移的作用。方法用电转染的方法建立稳定表达IP10的4T1细胞株IP10-4T1。将BALB/c小鼠分为IP10-4T1细胞组、4T1细胞组和转染pcDNA3的4T1细胞组(pcDNA3-4T1)。利用实验性肺转移模型和体外杀伤实验研究接种IP10-4T1对4T1细胞播散转移的影响。结果IP10-4T1细胞中IP10mRNA转录水平相对含量为0.92±0.12与未转染的4T1细胞(0.35±0.12)和pcDNA3-4T1细胞(0.29±0.08)比较差异有统计学意义(P<0.01)。IP10-4T1组对淋巴细胞的趋化指数为2.77±0.29,经CXCR3抗体处理后下降为1.71±0.20(P<0.05)。实验性肺转移结果显示,IP10-4T1组小鼠肺重为0.27g±0.02g,与4T1细胞组(0.48g±0.08g)和pcDNA3-4T1组(0.43g±0.16g)比较明显减轻(P=0.021);其肺表面形成的转移结节数较对照组少;IP10-4T1组肺组织中形成的4T1细胞克隆数为2.6±1.7,明显低于4T1组(34.0±6.3)和pcDNA3-4T1组(33.0±2.3,P<0.05);2/6的IP10-4T1组小鼠肺组织内可见转移灶,而对照组全部形成肺转移灶。接种IP10-4T1细胞组小鼠的淋巴细胞杀伤率在各个效/靶比均高于对照组(P<0.05)。结论增加肿瘤局部IP10的表达,能增强机体细胞免疫应答水平,通过肿瘤特异性的杀伤作用,抑制肿瘤细胞在体内播散转移。 Objective To observe the effect of enhancing the expression of IP10 in tumor site on the distant metastasis of breast cancer cell line 4T1. Methods The 4T1 cell line IP10-4T1 stably expressing IP10 was established by electroporation. BALB / c mice were divided into IP10-4T1 cell group, 4T1 cell group and 4T1 cell group (pcDNA3-4T1) transfected with pcDNA3. The effects of IP10-4T1 on the proliferation and metastasis of 4T1 cells were studied by experimental lung metastasis model and in vitro killing experiment. Results The relative level of IP10 mRNA transcription in IP10-4T1 cells was 0.92 ± 0.12, which was significantly different from that of untransfected 4T1 cells (0.35 ± 0.12) and pcDNA3-4T1 cells (0.29 ± 0.08) (P <0.01). The chemotactic index of lymphocytes in IP10-4T1 group was 2.77 ± 0.29, decreased to 1.71 ± 0.20 (P <0.05) after treated with CXCR3 antibody. The results of experimental lung metastasis showed that the lung weight of mice in IP10-4T1 group was 0.27g ± 0.02g, which was significantly reduced compared with 4T1 cell group (0.48g ± 0.08g) and pcDNA3-4T1 group (0.43g ± 0.16g) (P = 0.021). The number of metastatic nodules in the lung surface was less than that in the control group. The number of 4T1 cells in IP10-4T1 group was 2.6 ± 1.7, which was significantly lower than that in 4T1 group (34.0 ± 6.3) and pcDNA3-4T1 Group (33.0 ± 2.3, P <0.05). In 2/6 IP10-4T1 mice, metastases were found in the lungs, while those in the control group all formed lung metastases. The lymphocyte killing rate of mice inoculated with IP10-4T1 cells were higher than that of the control group at each efficiency / target ratio (P <0.05). Conclusion Increasing the expression of IP10 in the tumor can enhance the level of cellular immune response and inhibit tumor cell proliferation and metastasis in vivo through tumor-specific killing.
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