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培养的胰腺癌对天冬酰胺酶敏感性的机制

Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase.

作者信息

Wu M C, Arimura G K, Yunis A A

出版信息

Int J Cancer. 1978 Dec;22(6):728-33. doi: 10.1002/ijc.2910220615.

DOI:10.1002/ijc.2910220615
PMID:363626
Abstract

The effects of E. coli L-asparaginase on cultured human pancreatic carcinoma (MIA PaCa-2) have been studied. The enzyme (1 U/ml) inhibited growth and protein synthesis in both MIA PaCa-2 and PANC-1, another pancreatic carcinoma cell line, but had little or no effect on human breast carcinoma or melanoma cells. The inhibition of protein synthesis by E. coli L-asparaginase was largely reversed by L-glutamine but not by L-asparagine. The growth of both MIA PaCa-2 and PANC-1 showed absolute dependence on L-glutamine. These results indicate that the effect of E. coli L-asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L-glutaminase activity. Although the addition of L-glutamine to the culture appeared to prevent cell death caused by L-asparaginase, it did not restore the ability of the cells to proliferate. Asparaginase derived from vibrio succinogenes, which is virtually free of L-glutaminase activity, was equally inhibitory to MIA PaCa-2 cell growth but did not affect protein synthesis. It is concluded that the inhibition of growth of cultured pancreatic carcinoma cells by E. coli asparaginase is a combined function of both its L-asparaginase and L-glutaminase activity.

摘要

已对大肠杆菌L-天冬酰胺酶对培养的人胰腺癌(MIA PaCa-2)的作用进行了研究。该酶(1 U/ml)抑制了MIA PaCa-2和另一种胰腺癌细胞系PANC-1的生长及蛋白质合成,但对人乳腺癌或黑色素瘤细胞几乎没有影响。大肠杆菌L-天冬酰胺酶对蛋白质合成的抑制作用在很大程度上可被L-谷氨酰胺逆转,但不能被L-天冬酰胺逆转。MIA PaCa-2和PANC-1的生长均表现出对L-谷氨酰胺的绝对依赖性。这些结果表明,大肠杆菌L-天冬酰胺酶对培养的胰腺癌细胞的作用至少部分是通过其L-谷氨酰胺酶活性发挥的。尽管向培养物中添加L-谷氨酰胺似乎可防止由L-天冬酰胺酶引起的细胞死亡,但它并未恢复细胞的增殖能力。源自产琥珀酸弧菌的天冬酰胺酶几乎没有L-谷氨酰胺酶活性,它对MIA PaCa-2细胞生长同样具有抑制作用,但不影响蛋白质合成。得出的结论是,大肠杆菌天冬酰胺酶对培养的胰腺癌细胞生长的抑制作用是其L-天冬酰胺酶和L-谷氨酰胺酶活性的综合作用。

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J Exp Med. 1968 Jun 1;127(6):1055-72. doi: 10.1084/jem.127.6.1055.

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