Interleukin-10 gene transfer to peritoneal mesothelial cells suppresses peritoneal dissemination of gastric cancer cells due to a persistently high concentration in the peritoneal cavity

被引：17

作者：

Tanaka, F. ^{[1
]}

Tominaga, K. ^{[1
]}

Shiota, M. ^{[2
]}

Ochi, M. ^{[1
]}

Kuwamura, H. ^{[1
]}

Tanigawa, T. ^{[1
]}

Watanabe, T. ^{[1
]}

Fujiwara, Y. ^{[1
]}

Oshitani, N. ^{[1
]}

Higuchi, K. ^{[1
]}

Iwao, H. ^{[2
]}

Arakawa, T. ^{[1
]}

机构：

[1] Osaka City Univ, Grad Sch Med, Dept Gastroenterol, Abeno Ku, Osaka 5458585, Japan

[2] Osaka City Univ, Grad Sch Med, Dept Pharmacol, Osaka 5458585, Japan

来源：

CANCER GENE THERAPY | 2008年 / 15卷 / 01期

关键词：

interleukin-10; peritoneal mesothelial cells; peritoneal dissemination; gastric cancer;

D O I：

10.1038/sj.cgt.7701104

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Interleukin (IL)-10 has potent biological properties including an inhibitory action on the proliferation and metastasis of various cancer cells. However, it is difficult to maintain a high concentration of this cytokine as it has a short half life. In this study, we evaluated whether peritoneal mesothelial cells (PMCs) could be suitable for maintaining a high concentration of IL-10 using adenoviral gene transfer. We also evaluated the therapeutic effects of an intraperitoneal injection with adenoviral vector containing mouse IL-10 gene (Ad-mIL-10) using a mouse peritoneal dissemination model of MKN45 gastric cancer cells. We demonstrated that in vitro transfection efficiency of a recombinant adenovirus containing the bacterial beta-galactosidase gene (Ad-LacZ) was approximately 10-fold higher for primarily isolated PMCs than MKN45. The entire peritoneum was transfected until 3 weeks after an intraperitoneal Ad-LacZ injection. Ad-mIL-10 treatment increased intraperitoneal IL-10 levels until 3 weeks after treatment, and then significantly inhibited peritoneal cancer growth by inhibiting angiogenesis. This treatment also improved cachexia and prolonged mice survival. We thus concluded that IL-10 gene transfer in PMCs could be a new strategy for the prevention of peritoneal dissemination of gastric cancer due to the resulting persistently high IL-10 concentration in the peritoneal cavity.

引用

页码：51 / 59

页数：9

共 36 条

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