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

Rie Natatsuka, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Tomohiro Ookawara, Toshirou Nishida, Hisashi Hara, Takahiko Nishigaki, Emi Harada, Takashi Murakami, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Tadamitsu Kishimoto, Masaki Mori, Yuichiro DokiTetsuji Naka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 cycle-associated 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.

Original languageEnglish
Pages (from-to)433-442
Number of pages10
JournalBritish journal of cancer
Volume113
Issue number3
DOIs
Publication statusPublished - Jul 28 2015
Externally publishedYes

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Genetic Therapy
Stomach Neoplasms
Cytokines
Carcinoma
Cell Cycle
Ataxia Telangiectasia
Therapeutic Uses
Therapeutics
Photons
Heterografts
Neoplasms
Weights and Measures
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Natatsuka, R., Takahashi, T., Serada, S., Fujimoto, M., Ookawara, T., Nishida, T., ... Naka, T. (2015). Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis. British journal of cancer, 113(3), 433-442. https://doi.org/10.1038/bjc.2015.229

Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis. / Natatsuka, Rie; Takahashi, Tsuyoshi; Serada, Satoshi; Fujimoto, Minoru; Ookawara, Tomohiro; Nishida, Toshirou; Hara, Hisashi; Nishigaki, Takahiko; Harada, Emi; Murakami, Takashi; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Yamasaki, Makoto; Miyata, Hiroshi; Nakajima, Kiyokazu; Takiguchi, Shuji; Kishimoto, Tadamitsu; Mori, Masaki; Doki, Yuichiro; Naka, Tetsuji.

In: British journal of cancer, Vol. 113, No. 3, 28.07.2015, p. 433-442.

Research output: Contribution to journalArticle

Natatsuka, R, Takahashi, T, Serada, S, Fujimoto, M, Ookawara, T, Nishida, T, Hara, H, Nishigaki, T, Harada, E, Murakami, T, Miyazaki, Y, Makino, T, Kurokawa, Y, Yamasaki, M, Miyata, H, Nakajima, K, Takiguchi, S, Kishimoto, T, Mori, M, Doki, Y & Naka, T 2015, 'Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis', British journal of cancer, vol. 113, no. 3, pp. 433-442. https://doi.org/10.1038/bjc.2015.229
Natatsuka, Rie ; Takahashi, Tsuyoshi ; Serada, Satoshi ; Fujimoto, Minoru ; Ookawara, Tomohiro ; Nishida, Toshirou ; Hara, Hisashi ; Nishigaki, Takahiko ; Harada, Emi ; Murakami, Takashi ; Miyazaki, Yasuhiro ; Makino, Tomoki ; Kurokawa, Yukinori ; Yamasaki, Makoto ; Miyata, Hiroshi ; Nakajima, Kiyokazu ; Takiguchi, Shuji ; Kishimoto, Tadamitsu ; Mori, Masaki ; Doki, Yuichiro ; Naka, Tetsuji. / Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis. In: British journal of cancer. 2015 ; Vol. 113, No. 3. pp. 433-442.
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AU - Fujimoto, Minoru

AU - Ookawara, Tomohiro

AU - Nishida, Toshirou

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AU - Kurokawa, Yukinori

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AU - Nakajima, Kiyokazu

AU - Takiguchi, Shuji

AU - Kishimoto, Tadamitsu

AU - Mori, Masaki

AU - Doki, Yuichiro

AU - Naka, Tetsuji

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