Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis

被引：22

作者：

Natatsuka, Rie ^{[1
,2
]}

Takahashi, Tsuyoshi ^{[1
,2
]}

Serada, Satoshi ^{[2
]}

Fujimoto, Minoru ^{[2
]}

Ookawara, Tomohiro ^{[2
]}

Nishida, Toshirou ^{[3
]}

Hara, Hisashi ^{[1
,2
]}

Nishigaki, Takahiko ^{[1
,2
]}

Harada, Emi ^{[2
]}

Murakami, Takashi ^{[4
]}

Miyazaki, Yasuhiro ^{[1
]}

Makino, Tomoki ^{[1
]}

Kurokawa, Yukinori ^{[1
]}

Yamasaki, Makoto ^{[1
]}

Miyata, Hiroshi ^{[1
]}

Nakajima, Kiyokazu ^{[1
]}

Takiguchi, Shuji ^{[1
]}

Kishimoto, Tadamitsu ^{[5
]}

Mori, Masaki ^{[1
]}

Doki, Yuichiro ^{[1
]}

Naka, Tetsuji ^{[2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, Suita, Osaka 5650871, Japan

[2] Natl Inst Biomed Innovat, Lab Immune Signal, Ibaraki, Osaka 5670085, Japan

[3] Natl Canc Ctr Hosp East, Dept Surg, Kashiwa, Chiba 2778577, Japan

[4] Takasaki Univ Hlth & Welf, Dept Pharm, Takasaki, Gunma 3700033, Japan

[5] Osaka Univ, Immunologu Frontier Res Ctr, Lab Immune Regulat, Suita, Osaka 5650871, Japan

来源：

BRITISH JOURNAL OF CANCER | 2015年 / 113卷 / 03期

关键词：

gastric cancer; suppressor of cytokine signalling; ataxia telangiectasia and Rad3-related protein; cell cycle arrest; adenovirus vector; gene therapy; peritoneal carcinomatosis; DNA-DAMAGE CHECKPOINTS; PHASE-III; S-1; CHEMOTHERAPY; CISPLATIN; P53; HYPERMETHYLATION; METASTASIS; ACTIVATION; MECHANISMS;

D O I：

10.1038/bjc.2015.229

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Suppressor of cytokine signaling1 (SOCS1) is a negative regulator of various cytokines. Recently, it was investigated as a therapeutic target in various cancers. However, the observed antitumour effects of SOCS1 cannot not be fully explained without taking inhibition of proliferation signalling into account. Our aim was to discover a new mechanism of antitumour effects of SOCS1 for gastric cancer (GC). Methods: We analysed the mechanism of antitumour effect of SOCS1 in vitro. In addition, we evaluated antitumour effect for GC using a xenograft peritoneal carcinomatosis mouse model in preclinical setting. Results: We confirmed that SOCS1 suppressed proliferation in four out of five GC cell lines. SOCS1 appeared to block proliferation by a new mechanism that involves cell cycle regulation at the G2/M checkpoint. We showed that SOCS1 influenced cell cycleassociated molecules through its interaction with ataxia telangiectasia and Rad3-related protein. The significant difference in therapeutic effects was noted in terms of the post-treatment weight and total photon count of the intra-abdominal tumours. Conclusion: Forced expression of SOCS1 revealed a heretofore-unknown mechanism for regulating the cell cycle and may represent a novel therapeutic approach for the treatment of peritoneal carcinomatosis of GC.

引用

页码：433 / 442

页数：10

共 37 条

[1]

Bentley NJ, 2008, CLIN TRANSL ONCOL, V10, P538

[2] Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance [J].