新城疫病毒抗人急性单核细胞白血病作用的实验研究

Roles of Newcastle disease virus in human acute monocytic leukemia in vitro and in vivo

摘要:

目的：研究显示新城疫病毒(NDV)在对转移的黑色素瘤、高分化肾细胞癌等肿瘤的治疗中已经取得了良好的临床效果。本研究通过体内及体外实验初步探讨NDV对人急性单核细胞白血病的作用。方法：体外实验观察NDV感染组和对照组，即NDV感染或未感染急性单核细胞白血病细胞株SHI-1形态和密度变化，MTT 法测定 NDV 对细胞增殖的影响。体内实验通过建立裸鼠异种移植瘤模型，瘤内注射 NDV，计算抑瘤率，并评估NDV在体内的毒性作用。结果：倒置显微镜下，对照组细胞形态规则、分布密集；NDV 感染组细胞形态不规则，聚集、融合现象明显，分布稀疏。MTT检测结果显示不同浓度NDV对SHI-1细胞的增殖均有明显抑制作用（P<0.01），并呈现时间浓度依赖关系。NDV对SHI-1裸鼠异种移植瘤的抑制率为 84.7%，明显高于对照组（P<0.01）。实验过程中裸鼠无毒性反应。结论：NDV 在体内及体外均有抑制白血病细胞增殖的作用，并具有良好的安全性。

Abstract:

OBJECTIVE: Some research has shown that Newcastle disease virus (NDV) is effective in the treatment of various tumors, including transferred melanoma and well differentiated renal cell carcinoma. This study aimed to evaluate the effect of NDV against human acute monocytic leukemia SHI-1 cells in vitro and in vivo. METHODS: In vitro, the density and morphologic changes between wild SHI-1 cells (control) and NDV-infected SHI-1 cells were observed. MTT assay was utilized to observe the effect of NDV on the proliferation of SHI-1 cells. In vivo, the effect of NDV on the tumor inhibition was assessed using SHI-1 xenografts subcutaneously established in CD-1 nude mice. NDV was given by intra-tumor injections, and the tumor inhibition rate and toxic effects were evaluated. RESULTS: In the control group, the SHI-1 cells were observed using an inverted microscope to be regular in morphology and intensive in distribution. In the NDV-infected group, the SHI-1 cells were irregular and sparsate, and the aggregate and fused cells were common. MTT assay showed that the proliferation of SHI-1 cells were significantly inhibited by NDV at different concentrations (P<0.01) and in a time- and concentration-dependent manner. The tumor inhibition rate in the NDV group was 84.7%, which was significantly higher than that in the control group (P<0.01). No toxic effects were observed in the nude mice. CONCLUSIONS: NDV can suppress the proliferation of human acute monocytic leukemic cells both in vitro and in vivo. The safety of NDV is reliable.