NK4 growth inhibition of human Raji lymphoma xenografts by competitive interrupting HGF/Met signal pathway / 中华病理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the inhibition of NK4 protein in the proliferation of human Raji lymphoma xenografts in nude mice, and to explore its molecular mechanism.</p><p><b>METHODS</b>Models of human Raji lymphoma xenograft transfected with HGF gene were established by subcutaneous inoculation in nude mice. After establishment of the models, the mice received continuous NK4 protein via tail vein for 4 weeks, and the weight and tumor growth were monitored every week. After 8 weeks, the expression of HGF mRNA and c-Met mRNA of tumor tissues was measured by real-time fluorescent quantitation PCR. The apoptotic index (AI) and microvessel density (MVD) were evaluated by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and immunohistochemistry, respectively.</p><p><b>RESULTS</b>The models of human Raji lymphoma xenograft were successfully established. Although the animal weights of all groups declined, especially in the groups with NK4 protein injection, there was no statistical significance (P > 0.05). The tumor volume in HGF gene transfected group was larger than those of the control groups (P < 0.01), and there was no statistical significance among the control groups (P > 0.05). However, the tumor volume of the NK4 protein injection group decreased significantly (P < 0.01). Expression of HGF mRNA and c-Met mRNA in HGF gene transfected group increased significantly after injection of NK4 protein (P < 0.01). AI in HGF gene transfected group (33.5% ± 12.3%) was significantly lower than that of control groups (89.1% ± 22.3% vs. 81.9% ± 27.0%, P < 0.05), but became significantly higher (119.1% ± 18.9%) after NK4 protein injection (P < 0.01). MVD in HGF gene transfected group (28.5 ± 2.0) was higher than that of control groups (12.2 ± 1.4, 13.8 ± 1.3, P < 0.01), although declined (15.5 ± 2.5) after NK4 protein injection (P < 0.01).</p><p><b>CONCLUSIONS</b>NK4 protein suppresses significantly the growth of human Raji lymphoma xenografts transfected with HGF gene. The pathogenesis may be involved in promoting tumor cell apoptosis and restraining tumor angiogenesis through competitive interrupting HGF/Met signal pathway.</p>