Swainsonine augments the cytotoxicity of human lymphokine-activated killer cells against autologous thyroid cancer cells.
Swainsonine augments the cytotoxicity of human lymphokine-activated killer cells against autologous thyroid cancer cells.
复制标题
苦马豆素增强人淋巴因子激活的杀伤细胞对自体甲状腺癌细胞的细胞毒性。
DOI：
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
M. Yagita
中科院分区：
文献类型：
--
作者：
S. Fujieda;I. Noda;H. Saito;T. Hoshino;M. Yagita
客观化
苦马豆素(Swainsonine，Sw)是一种哺乳动物高尔基体α-甘露糖苷酶II的抑制剂，它能阻止高甘露糖向复合型低聚糖的转化。本研究探讨了顺铂对淋巴因子激活的杀伤细胞(LAK)杀伤自体甲状腺癌细胞毒作用的影响。
设计
将甲状腺癌患者外周血淋巴细胞与重组白介素2(100U/m L)和重组人白介素2(0.5 mg/L)共同孵育7d，取手术标本甲状腺癌细胞用白藜芦醇(0.5 mg/L)预处理18h。用标准的4小时放射性铬-51释放法检测经SW处理的LAK细胞对肿瘤细胞的细胞毒作用。
结果
经SW处理的LAK细胞对自体甲状腺癌细胞的杀伤作用明显强于单独用IL-2孵育的标准LAK细胞。短波处理后，LAK细胞的N-α-苄氧羰基-L-赖氨酸硫代苯甲酸酯酶活性也增加，这种活性是致死阶段所必需的细胞毒因子。此外，与未经处理的肿瘤细胞相比，与未处理的肿瘤细胞相比，与SW孵育的甲状腺癌细胞对LAK杀伤的敏感性要高得多。
结论
我们的结果提示，SW可能在甲状腺癌的治疗中具有潜在的免疫调节作用。
OBJECTIVE
Swainsonine (SW), an inhibitor of mammalian Golgi alpha-mannosidase II, blocks the processing of high mannose to complex type oligosaccharides. In this study, the effect of SW on the cytotoxicity of lymphokine-activated killer (LAK) cells against autologous thyroid cancer was investigated.
DESIGN
Peripheral blood lymphocytes from patients with thyroid cancer were incubated with recombinant interleukin 2 (100 U/mL) and 0.5 mg/L of SW for 7 days, and thyroid cancer cells obtained from surgical specimens were pretreated with SW (0.5 mg/L) for 18 hours. The cytotoxicity of SW-treated LAK cells against tumor cells tested in a standard 4-hour radioactive chromium Cr 51 release assay.
RESULTS
The cytotoxicity of SW-treated LAK cells against autologous thyroid cancer cells was found to be significantly greater than that of standard LAK cells incubated with interleukin 2 alone. The N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester esterase activity of LAK cells, this activity being a cytotoxic factor that is necessary for the lethal hit stage, was also increased by SW treatment. Further, thyroid cancer cells incubated with SW, as compared with nontreated tumor cells, showed much higher susceptibility to LAK killing.
CONCLUSIONS
Our results suggest that SW might have potential immunomodulatory properties in the treatment of thyroid cancer.
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