A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells

经过修饰的精氨酸消耗酶 NEI-01 可抑制胰腺癌细胞的生长

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作者:Jeremy P H Chow, Yijun Cai, Daniel T L Chow, Steven H K Chung, Ka-Chun Chau, Ka-Ying Ng, Oscar M Leung, Raymond M H Wong, Alan W L Law, Yu-On Leung, Sui-Yi Kwok, Yun-Chung Leung

Abstract

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

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