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背景与目的:NK4不仅是肝细胞生长因子的拮抗剂,而且是血管形成的抑制剂。研究已经证实NK4可以抑制肿瘤的生长和转移,但有关其在胰腺癌中的作用,目前少见文献报道。为此,本研究旨在探讨NK4基因在裸鼠体内的抗胰腺癌作用及其可能的机制。方法:建立裸鼠胰腺癌皮下移植瘤模型,构建NK4基因真核细胞表达载体并转染入瘤体内,转染前后称其体重、瘤重和测肿瘤体积,采用免疫组织化学和脱氧核糖核酸末端转移酶介导的缺口末端标记技术对裸鼠胰腺癌组织中的凋亡细胞、增殖抗原和微血管密度进行观察和比较。结果:4周后,NK4转染组裸鼠移植瘤体积为(1.39±0.33)cm3,明显小于对照组和空载体组[(2.06±0.55)cm3和(1.90±0.36)cm3,P<0.01];其瘤重为(1.30±0.81)g,也显著低于对照组和空载体组[(3.45±1.88)g和(3.14±1.51)g,P<0.01],抑瘤率为62.29%。NK4转染组肿瘤细胞的凋亡指数为9.34±0.91,显著高于对照组和空载体组(4.13±0.79和3.94±1.03,P<0.001);而NK4转染组肿瘤细胞的增殖指数为53.88±4.30,与对照组间和空载体组比较无显著性差异(56.24±4.03和54.33±5.41,P>0.05);NK4转染组肿瘤组织的微血管密度为(12.24±4.63),明显低于对照组和空载体组(20.13±7.00和19.70±6.15,P<0.05)。结论:转染NK4基因可显著抑制裸鼠胰腺癌移植瘤的生长,其作用机制可能是通过抑制肿瘤新生血管的形成,促进肿瘤细胞凋亡。
Background and Objective: NK4 is not only an antagonist of hepatocyte growth factor, but also an inhibitor of angiogenesis. Studies have confirmed that NK4 can inhibit tumor growth and metastasis, but its role in pancreatic cancer, it is rarely reported in the literature. Therefore, this study aimed to investigate the anti-pancreatic cancer effect and its possible mechanism of NK4 gene in nude mice. METHODS: The subcutaneous xenograft model of pancreatic cancer in nude mice was established. The eukaryotic expression vector of NK4 gene was constructed and transfected into the tumor. The body weight, tumor weight and tumor volume were measured before and after transfection. Immunohistochemistry and DNA end Transferase-mediated nick end labeling technique was used to observe and compare the apoptotic cells, proliferation antigens and microvessel density in pancreatic cancer tissue of nude mice. Results: After 4 weeks, the volume of transplanted tumor in NK4 transfection group was (1.39 ± 0.33) cm3, which was significantly lower than that in control group and empty vector group [(2.06 ± 0.55) cm3 and (1.90 ± 0.36) cm3, P <0.01] The tumor weight was (1.30 ± 0.81) g, which was also significantly lower than that in the control and empty vector groups (3.45 ± 1.88g and 3.14 ± 1.51g, P <0.01). The tumor inhibition rate was 62.29%. The apoptotic index of tumor cells in NK4 transfection group was 9.34 ± 0.91, which was significantly higher than that in control group and empty vector group (4.13 ± 0.79 and 3.94 ± 1.03, P <0.001), while the proliferation index of NK4 transfection group was 53.88 ± 4.30. There was no significant difference between control group and empty vector group (56.24 ± 4.03 and 54.33 ± 5.41, P> 0.05). The microvessel density of tumor tissue in NK4 transfected group was (12.24 ± 4.63), which was significantly lower than that of control Group and empty vector group (20.13 ± 7.00 and 19.70 ± 6.15, P <0.05). CONCLUSION: Transfection of NK4 gene can significantly inhibit the growth of transplanted pancreatic cancer in nude mice. Its mechanism may be through inhibiting the formation of tumor angiogenesis and promoting tumor cell apoptosis.