胃癌细胞对细小病毒H-1敏感性差异的实验研究

目的 探讨不同胃癌细胞株对细小病毒细胞毒作用的敏感性差异及可能的机制。方法共选用HGC27(未分化)、BGC823(未分化)、MKN45(低分化)、AGS(低分化)、SGC7901(中分化)和MKN28(高分化)等6株不同分化状态的胃癌细胞株，用流式细胞仪分析其各自的细胞周期，H-1病毒感染后采用MTT方法检测不同胃癌细胞株对其细胞毒作用的敏感性差异，用RT-PCR来检测H-1病毒中的非结构蛋白基因(NS-1)在6株不同胃癌细胞中的表达。结果 HGC27、BGC823、MKN45、AGS、SGC7901和MKN28等不同分化状态细胞株中，S期细胞的比率分别为24．72％，30．15％，27．10％，29．03％，31．82％和33．73％。其中HGC27细胞对H-1病毒的细胞毒作用敏感；SGC7901细胞其次；MKN45、AGS细胞对H-1病毒的细胞毒作用中等敏感；MKN28细胞对H-1病毒的细胞毒作用不敏感；而BGC823则对H-1病毒的细胞毒作用抵抗。病毒NS-1的mRNA在HGC27、BGC823、MKN45和SGC7901等细胞中的表达水平较高，而在AGS和MKN28中的表达水平却较低。结论 H-1病毒的细胞毒作用在不同的胃癌细胞株中的差异显著。总体上，与高分化细胞株MKN28细胞相比，分化差的细胞对细小病毒H-1的细胞毒作用敏感性增加。其机制至少部分与分化差细胞中病毒NS-1蛋白的产生和积聚能力增高相关。未分化的BGC823细胞对H-1病毒的细胞毒作用抵抗，进一步证实并非所有的肿瘤细胞都对细小病毒的溶胞性作用敏感。

Investigation on the sensitivities of distinct gastric cancer cells to parvovirus H-1 induced cytotoxicity

Objective To investigate the sensitivities of distinct gastric cancer cells to parvovirus H-1 induced cytotoxicity and its possible mechanisms. Methods Six distinct differentiated gastric cancer cell lines were employed in this study, including HGC27 (undifferentiated), BGC823(undifferentiated), MKN45(poor differentiated), AGS (poor differentiated), SGC7901(moderate differentiated) and MKN28 (well differentiated). The cell cycle distributions were measured by flow cytometry. The differential sensitivities of six distinct gastric cancer cells after H-1 virus infection were detected by MTT analysis. The RT-PCR was employed to detect viral NS-1 gene expression in all six gastric cancer cell lines. Results The S phase ratios of HGC27, BGC823, MKN45, AGS, SGC7901 and MKN28 were 24.72%, 30.15%, 27.10%, 29.03%, 31.82% and 33.73% respectively. HGC27 cells were sensitive to H-1 virus induced cytotoxicity followed by SGC7901 cells. MKN45 and AGS cells were moderately sensitive. MKN28 cells were insensitive. However, BGC823 cells were resistant to H-1 virus induced cytotoxicity. The expressions of viral NS-1 were higher in HGC27, BGC823, MKN45 and SGC7901 cells, whilst NS-1 gene expressions were lower in AGS and MKN28 cells. Conclusions The sensitivities of distinct gastric cancer cells to H-1 virus induced cytotoxicity could be markedly different. In general, the poorly differentiated cells showed an enhanced sensitivity to H-1 virus attack as compared to well differentiated ones. The enhanced sensitivity of poorly-versus well-differentiated gastric cancer cells to H-1 virus is due to at least in part, to the enhanced capacity of the former cells for NS-1 protein production and accumulation. The undifferentiated BGC823 cells were resistant to H-1 virus triggered cytotoxicity. It may further verify that not all the tumor cells were sensitive to H-1 virus lytic effects.