Establishment of order-made therapy by mediating cholesterol metabolism pathways in castration-resistant prostate cancer dells

• Project/Area Number: 26462432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Aichi Medical University
• Principal Investigator: Sumitomo Makoto 愛知医科大学, 医学部, 教授 (50255535)
• Research Collaborator: MURAMATSU HIROYUKI 愛知医科大学, 医学部, 助教 (60714847)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 去勢抵抗性前立腺癌 / 嫌気性解糖系 / 乳酸脱水素酵素 / アポトーシス / タキサン / アミノ酸トランスポーター / オートファジー / 前立腺癌 / docetaxel

Outline of Final Research Achievements

We investigated the role of LDH-A in mediating castration resistance of human prostate cancer (PC) cells by analyzing PC cell lines. LDH expression is strongly associated with docetaxel (DOC) sensitivity in PC cells. A specific LDH-A inhibitor sodium oxamate (SO) inhibited cell growth in PC cells, which was presumably caused by the inhibition of LDH-A protein expression. Synergistic cytotoxicity was observed after the combination therapy with DOC and SO in castration resistant LN-CSS cells, but not in parental LNCaP cells. The combination with DOC and SO caused cell cycle arrest in G2-M and SO promotes DOC-induced apoptosis in LN-CSS cells, which was partially caused by inhibition of DOC-induced increases in LDH-A expression. Our study may provide valuable information for the future development of targeted therapies for CRPC.

Research Products

• [Presentation] 前立腺癌細胞株に対するdocetaxelとLDH阻害薬による抗腫瘍効果の検討 (2018)
  • Author(s): 村松洋行, 住友 誠, 杉江美穂, 森永慎吾, 小林郁生, 梶川圭史, 西川源也, 加藤義晴, 渡邊將人, 全並賢二, 金尾健人, 中村小源太, 吉川和宏
  • Organizer: 第27回泌尿器科分子・細胞研究会
• [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetacel-induced cytotoxicity in prostate cancer cells (2018)
  • Author(s): Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Miho Sugie, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Yoshiharu Kato, Masahito Watanabe, Kenji Zennami, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa
  • Organizer: Annual meeting of European Association of Urology 2018
• [Presentation] 前立腺癌細胞株に対するLDH阻害薬とdocetaxelによる抗腫瘍効果の検討 (2017)
  • Author(s): 村松洋行, 住友 誠, 斎藤政信, 杉江美穂, 森永慎吾, 小林郁生, 梶川圭史, 西川源也, 加藤義晴, 渡邊將人, 金尾健人, 中村小源太, 吉川和宏
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetacel-induced cytotoxicity in prostate cancer cells. (2017)
  • Author(s): Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Masanobu Saito, Miho Sugie, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Yoshiharu Kato, Masahito Watanabe, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa
  • Organizer: AACR annual meeting 2017
• [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害薬の併用投与による抗腫瘍効果の検討 (2017)
  • Author(s): 村松洋行;住友誠;森永慎吾;梶川圭史;小林郁生;西川源也;加藤義晴;渡邊將人;金尾健人;中村小源太; 吉川和宏
  • Organizer: 第26回泌尿器科分子・
  • Place of Presentation: 大分
• [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetacel-induced cytotoxicity in prostate cancer cells. (2017)
  • Author(s): Hiroyuki Muramatsu,Makoto Sumitomo, Shingo Morinaga,Keishi Kajikawa,Ikuo Kobayashi,Genya Nishikawa,
  • Organizer: AACR Annual Meeting 2017
  • Place of Presentation: Washington DC
• [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害の併用投与による抗腫瘍効果の検討 (2016)
  • Author(s): 村松洋行、住友 誠、渡邊將人、森永慎吾、梶川圭史、小林郁生、西川源也、吉澤孝彦、加藤義晴、渡邊將人、金尾健人、中村小源太、吉川 和宏
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-22
• [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetaxel-induced cytotoxicity in prostate cancer cells. (2016)
  • Author(s): Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Takahiko Yoshizawa, Yoshiharu Kto, Masahito Watanabe, Kenji Zennami, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa.
  • Organizer: European urological association 30th Annual Congress
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2016-03-11
  • Int'l Joint Research
• [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害の併用投与による抗腫瘍効果の検討 (2016)
  • Author(s): 村松洋行、住友 誠、渡邊將人、森永慎吾、梶川圭史、小林郁生、西川源也、吉澤孝彦、加藤義晴、渡邊將人、金尾健人、中村小源太、吉川 和宏
  • Organizer: 第25回泌尿器科分子・細胞研究会
  • Place of Presentation: 大阪
  • Year and Date: 2016-02-06
• [Presentation] 前立腺癌細胞株におけるdocetaxelとLDH阻害薬の併用投与による抗腫瘍効果の検討 (2016)
  • Author(s): 村松洋行;住友誠;森永慎吾;梶川圭史;小林郁生;西川源也;吉澤孝彦;加藤義晴;渡邊將人;金尾健人;中村小源太; 吉川和宏
  • Organizer: 第104回日本泌尿器科学会
  • Place of Presentation: 仙台
• [Presentation] 前立腺癌の嫌気性解糖系に対するLDH阻害薬の細胞増殖抑制効果の検討 (2015)
  • Author(s): 村松洋行, 住友誠, 全並賢二, 森永慎吾, 梶川圭史, 小林郁生, 西川源也, 吉澤孝彦, 加藤義晴, 渡邊將人, 金尾健人, 中村小源太, 吉川和宏
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-21
• [Presentation] Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A promotes docetaxel-induced cytotoxicity in prostate cancer cells. (2015)
  • Author(s): Hiroyuki Muramatsu, Makoto Sumitomo, Kenji Zennami, Shingo Morinaga, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Takahiko Yoshizawa, Yoshiharu Kato, Masahito Watanabe, Kent Kanao, Kogenta Nakamura, Kazuhiro Yoshikawa
  • Organizer: 30th European Association Urology annual meeting
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2015-03-21
• [Presentation] 前立腺癌の嫌気性解糖系に対するLDH阻害薬の細胞増殖抑制効果の検討 (2015)
  • Author(s): 村松洋行, 住友誠, 全並賢二, 森永慎吾, 梶川圭史, 小林郁生, 西川源也, 吉澤孝彦, 加藤義晴, 渡邊將人, 金尾健人, 中村小源太, 吉川和宏
  • Organizer: 第２４回泌尿器分子・細胞研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-28