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Analysis of antitumor effect mechanism by dopamine signal inhibitor

Research Project

Project/Area Number 18K15223
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionTokyo University of Science

Principal Investigator

Okazaki Shogo  東京理科大学, 研究推進機構生命医科学研究所, 助教 (20784044)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords悪性腫瘍 / ドパミン / セロトニン / 口腔扁平上皮癌 / 酸化ストレス / 代謝
Outline of Final Research Achievements

In this study, I analyzed anti-tumor mechanism of dopamine signal inhibitors. I found that dopamine receptor antagonist induces accumulation of hydrogen peroxide in tumor cells.
This mechanism contributes to anti-tumor effect of dopamine receptor antagonist. Furthermore, I identified that antagonistic effect against serotonin receptors may also contributes to antitumor effect of dopamine receptor antagonist. This study revealed potential of dopamine/serotonin signal as novel tumor therapy target.

Academic Significance and Societal Importance of the Research Achievements

がん細胞における治療抵抗性は、臨床上の最も深刻な課題の一つである。本研究では、治療抵抗性癌細胞に対してドパミン受容体に対するアンタゴニストが抗腫瘍効果を示すという結果に基づき、腫瘍細胞におけるドパミン受容体の機能解析及びその抗腫瘍効果機序の解析を行った。その結果、ドパミン受容体アンタゴニストによる抗腫瘍効果機序の一端を明らかとし、また、ある種のセロトニン受容体についても悪性腫瘍の進展に寄与している可能性を見出した。この研究成果により、ドパミンおよびセロトニン受容体を標的とすることで新たな癌治療の開発への発展の可能性を示すことができた。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.2020

    • Author(s)
      Otsuki Y, Yamasaki J, Suina K, Okazaki S, Koike N, Saya H, Nagano O.
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 1 Pages: 127-136

    • DOI

      10.1111/cas.14224

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel functional anti-HER3 monoclonal antibodies with potent anti- cancer effects on various human epithelial cancers.2020

    • Author(s)
      Okita K, Okazaki S, Uejima S, Yamada E, Kaminaka H, Kondo M, Ueda S, Tokiwa R, Iwata R, Yamasaki A, Hayashi N, Ogura D, Hirotani K, Yoshioka T, Inoue M, Masuko K, Masuko T
    • Journal Title

      Oncotarget

      Volume: 11 Issue: 1 Pages: 31-45

    • DOI

      10.18632/oncotarget.27414

    • NAID

      120006888520

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endothelial-Mesenchymal Transition Drives Expression of CD44 Variant and xCT in Pulmonary Hypertension2019

    • Author(s)
      Isobe Sarasa、Kataoka Masaharu、Endo Jin、Moriyama Hidenori、Okazaki Shogo、Tsuchihashi Kenji、Katsumata Yoshinori、Yamamoto Tsunehisa、Shirakawa Kohsuke、Yoshida Naohiro、Shimoda Masayuki、Chiba Tomohiro、Masuko Takashi、Hakamata Yoji、Kobayashi Eiji、Saya Hideyuki、Fukuda Keiichi、Sano Motoaki
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: Volume61,Issue3 Issue: 3 Pages: 367-379

    • DOI

      10.1165/rcmb.2018-0231oc

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glutaminolysis-related genes determine sensitivity to xCT-targeted therapy in head and neck squamous cell carcinoma.2019

    • Author(s)
      Okazaki S, Umene K, Yamasaki J, Suina K, Otsuki Y, Yoshikawa M, Minami Y, Masuko T, Kawaguchi S, Nakayama H, Banno K, Aoki D, Saya H, Nagano O.
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 11 Pages: 3453-3463

    • DOI

      10.1111/cas.14182

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor Tlx1 marks a subset of lymphoid tissue organizer-like mesenchymal progenitor cells in the neonatal spleen2019

    • Author(s)
      Ueno Yuta、Fujisaki Keiko、Hosoda Shoko、Amemiya Yusuke、Okazaki Shogo、Notsu Chihiro、Nishiyama Chiharu、Mabuchi Yo、Matsuzaki Yumi、Oda Akihisa、Goitsuka Ryo
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20408-20408

    • DOI

      10.1038/s41598-019-56984-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulfasalazine could modulate the CD 44v9‐xCT system and enhance cisplatin‐induced cytotoxic effects in metastatic bladder cancer2019

    • Author(s)
      Ogihara Koichiro、Kikuchi Eiji、Okazaki Shogo、Hagiwara Masayuki、Takeda Toshikazu、Matsumoto Kazuhiro、Kosaka Takeo、Mikami Shuji、Saya Hideyuki、Oya Mototsugu
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 4 Pages: 1431-1441

    • DOI

      10.1111/cas.13960

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti‐tumor effects of mAb against l‐type amino acid transporter 1 (LAT1) bound to human and monkey LAT1 with dual avidity modes2019

    • Author(s)
      Ueda Shiho、Hayashi Hidemi、Miyamoto Takako、Abe Shinya、Hirai Kana、Matsukura Kanji、Yagi Hideki、Hara Yuta、Yoshida Kinji、Okazaki Shogo、Tamura Masakazu、Abe Yuki、Agatsuma Toshinori、Niwa Shin‐ichiro、Masuko Kazue、Masuko Takashi
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 2 Pages: 674-685

    • DOI

      10.1111/cas.13908

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthetic lethality of the ALDH3A1 inhibitor dyclonine and xCT inhibitors in glutathione deficiency-resistant cancer cells2018

    • Author(s)
      Okazaki Shogo、Shintani Subaru、Hirata Yuki、Suina Kentaro、Semba Takashi、Yamasaki Juntaro、Umene Kiyoko、Ishikawa Miyuki、Saya Hideyuki、Nagano Osamu
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 73 Pages: 33832-33843

    • DOI

      10.18632/oncotarget.26112

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EGFR promotes glioma progression by regulating xCT and GluN2B-containing NMDA receptor signaling.2018

    • Author(s)
      Suina K, Tsuchihashi K, Yamasaki J, Kamenori S, Shintani S, Hirata Y, Okazaki S, Sampetrean O, Baba E, Akashi K, Takahashi F, Takahashi K, Saya H, Nagano O.
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 12 Pages: 3874-3882

    • DOI

      10.1111/cas.13826

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Accumulation of leukemic cells to the spleen is regulated by a transcription factor Tlx1 expressed in perifollicular mesenchymal cells.2019

    • Author(s)
      Yusuke Amemiya, Shogo Okazaki, Chiharu Nishiyama, Takuro Nakamura and Ryo Goitsuka
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Genetic labeling of neonatal CXCR5-expressing cells for tracking long-lived B-1 cells in the adults.2019

    • Author(s)
      Keiko Fujisaki, Shogo Okazaki and Chiharu Nishiyama, Yohsuke Harada, and Ryo Goitsuka
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Recruitment of peritoneal B-1a cells to the spleen is regulated by the perifollicular mesenchymal niche.2019

    • Author(s)
      Shoko Hosoda, Shogo Okazaki and Chiharu Nishiyama and Ryo Goitsuka
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] FOXA1 expression confers resistance to xCT-targeted therapy in HNSCC2019

    • Author(s)
      Shogo Okazaki, Subaru Shintani, Hideyuki Saya and Osamu Nagano
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Extramedullary leukemogenic niche in the spleen exacerbates the progression of acute myeloid leukemia.2019

    • Author(s)
      Yusuke Amemiya, Shogo Okazaki, Takuro Nakamura and Ryo Goitsuka
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] xCT confers cancer stem like properties in small cell lung cancer cells.2019

    • Author(s)
      Kentaro Suina, Juntaro Yamasaki, Yuji Otsuki, Yuki Hirata, Shogo Okazaki, Kenji Tsuchihashi, Oltea Sampetrean, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kazuhisa Takahashi, Hideyuki Saya, Osamu Nagano
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Benzaldehyde activates AMPK via cancer specific upregulated 14-3-3ζ2019

    • Author(s)
      7.Jun Saitoh, Nobuyuki Onishi, Eiji Sugihara, Takatsune Simizu, Kiyomi Kimura, Naoyoshi Koike, Oltea Sampetrean, Shogo Okazaki, Hiroyuki Nobusue, Takashi Kasama, Hideyuki Saya
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脾臓微小環境による骨髄自然制御性プラズマブラストの分化・移行制御2019

    • Author(s)
      藤崎桂子、西山千春、岡崎章悟、後飯塚僚
    • Organizer
      第29回Kyoto T cell conference (KTCC)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 転写因子Tlx1を発現する成体脾臓微小環境による腹腔B-1a細胞の脾臓への移行制御2019

    • Author(s)
      細田祥子、藤崎桂子、西山千春、原田陽介、岡崎章悟、後飯塚僚
    • Organizer
      第29回学術集会Kyoto T cell conference (KTCC)
    • Related Report
      2019 Annual Research Report
  • [Presentation] BRD4 regulates the expression of Livin and thereby confers resistance to Fas-mediated immune cytotoxicity in aggressive B-cell lymphoma.2019

    • Author(s)
      Sugihara Eiji, Norisato Hashimoto, Satoru Osuka, Sayaka Ueno, Takatsune Shimizu, Shogo Okazaki, Taka-aki Sato, Shinichiro Okamoto, Hideyuki Saya
    • Organizer
      AACR Annual Meeting 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] SLC7A11 expression confers cancer stem-like properties in small cell lung cancer cells.2019

    • Author(s)
      Shohei Kamenori, Kentaro Suina, Juntaro Yamasaki, Subaru Shintani, Yuji Otsuki, Yuki Hirata, Shogo Okazaki, Kenji Tsuchihashi,Oltea Sampetrean, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kazuhisa Takahashi, Hideyuki Saya, Osamu Nagano
    • Organizer
      AACR Annual Meeting 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Combinatorial inhibition of xCT and ALDH3A1 induces synthetic lethality in xCT inhibitor-resistant cancer cells2018

    • Author(s)
      Shogo Okazaki, Subaru Shintani, Yuki Hirata, Hideyuki Saya, Osamu Nagano
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Benzaldehyde inhibits the multiple signals and E2F transcription in cancer cells by suppression of overexpressed 14-3-3ζ2018

    • Author(s)
      Jun Saitoh, Nobuyuki Onishi, Eiji Sugihara, Shogo Okazaki, Hiroyuki Nobusue, Takashi Kasama, Hideyuki Saya
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] A novel gastric cancer mouse model by using organoid technique and genetic manipulation2018

    • Author(s)
      Yuki Hirata, Osamu Nagano, Yoshiyuki Saito, Juntaro Yamasaki, Subaru Shintani, Kentaro Suina, Shogo Okazaki, Hirofumi Kawakubo, Hideyuki Saya, Yuko Kitagawa
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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