Molecular basis for the induction of vaults by anti-cancer agents, and the role of vaults in resistance to anti-cancer agents.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590168
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kagoshima University
• Principal Investigator: YAMADA Katsushi 鹿児島大学, 医歯学総合研究科, 客員研究員 (00037491)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Yasuo 鹿児島大学, 医学部・歯学部附属病院, 教授 (60245462) ; IKEDA Ryuji 鹿児島大学, 医学部・歯学部附属病院, 副薬剤部長 (50398278)
• Project Period (FY): 2009 – 2011
• Keywords: Vaults / 抗がん剤耐性 / apoptosis / caspase / adriamycin / major vault protein / Sp-1

Research Abstract

The major vault protein(MVP) is the main constituent of the vault ribonucleoprotein particle. Although the role in multidrug resistance has been suggested, the physiological function of vaults remains unclear. It has been reported that MVP levels were elevated after treatment with the DNA-damaging agents such as adriamycin(ADR). The aim of this study was to investigate molecular basis for the induction of MVP by ADM, and to investigate the potential role of MVP in drug resistance. Expression levels of both MVP protein and MVP mRNA were increased by ADM. ADM could also enhance MVP promoter activity. Introduction of siRNA against Sp-1 in SW620cells attenuated the expression of MVP induced by ADM. Down-regulation of MVP expression by MVP RNAi in SW620cells increased the sensitivity of the cells to ADM. Furthermore, ADM enhanced the activation of caspase 3 and caspase 8 in the MVP knock-down cells, but not in control cells. Our data demonstrate that exposure of cancer cells to DNA-damaging agents induces MVP that might have an important role in the resistance to chemotherapeutic agents.

Research Products

• [Journal Article] Thymidine phosphorylase activity is involved in augmented reactive oxygen species and interleukin-8 production in human cancer cells (2012)
  • Author(s): Tabata, S., Ikeda, R., Yamamoto, M., Furukawa, T., Kuramoto, T., Takeda, Y., Yamada, K., Haraguchi, M., Nishioka, Y., Sone, S., Akiyama, S.
  • Journal Title: Oncology Reports Volume: (in press)
  • Peer Reviewed
• [Journal Article] Analysis of the outcome of concurrent neoadjuvant chemoradiotherapy with S-1 compared to super-selective intra-arterial infusion for oral squamous cell carcinoma (2012)
  • Author(s): Miyawaki, A., Hijioka, H., Ikeda, R., Ishida, T., Nozoe, E., Nakamura, N.
  • Journal Title: Oncology letters Volume: (in press)
  • Peer Reviewed
• [Journal Article] Safety analysis of liposomal amphotericin B in adult patients : anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia (2011)
  • Author(s): Shigemi, A., Matsumoto, K., Ikawa, K., Yaji, K., Shimodozono, Y., Morikawa, N., Takeda, Y., Yamada, K.
  • Journal Title: International Journal of Antimicrobial Agents Volume: 38 Pages: 417-420
  • Peer Reviewed
• [Journal Article] Effect of 5-fluorouracil treatment on SN-38absorption from intestine in rats (2011)
  • Author(s): Shibayama, Y., Iwashita, Y., Yoshikawa, Y., Kondo, T., Ikeda, R., Takeda, Y., Osada, T., Sugawara, M., Yamada, K., Iseki, K.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 34 Pages: 1418-1425
  • Peer Reviewed
• [Journal Article] Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib (2011)
  • Author(s): Shibayama, Y., Nakano, K., Maeda, H., Taguchi, M., Ikeda, R., Sugawara, M., Iseki, K., Takeda, Y., Yamada, K.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 34 Pages: 433-435
  • Peer Reviewed
• [Journal Article] Isolation and Characterization of Gemcitabine-resistant in Human Non-small Cell Lung Cancer A549cells (2011)
  • Author(s): Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Sachidanandam, K., Yamada, K., Kolesar, J. M.
  • Journal Title: International Journal of Oncology Volume: 38 Pages: 513-519
  • Peer Reviewed
• [Journal Article] Isolation and Characterization of Erlotinib-resistant in Human Non-small Cell Lung Cancer A549cells (2011)
  • Author(s): Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Kavanaugh, S. M., Yamada, K., Kolesar, J. M.
  • Journal Title: Oncology Letters Volume: 2 Pages: 91-94
  • Peer Reviewed
• [Journal Article] p53 Plays an Important Role in Cell Fate Determination after Exposure to Microcystin-LR (2010)
  • Author(s): Takumi, S., Komatsu, M., Furukawa, T., Ikeda, R., Sumizawa, T., Akenaga, H., Maeda, Y., Aoyama, K., Arizono, K., Ando, S., Takeuchi T.
  • Journal Title: Environmental Health Perspectives Volume: 118 Pages: 1292-1298
  • Peer Reviewed
• [Journal Article] SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma (2010)
  • Author(s): Miyawaki, A., Ikeda, R., Hijioka, H., Ishida, T., Ushiyama, M., Nozoe, E., Nakamura, N.
  • Journal Title: Oncology Reports Volume: 23 Pages: 1205-1212
  • Peer Reviewed
• [Journal Article] Alternative Splicing of the Pituitary Adenylate Cyclase-activating Polypetide(PACAP) Receptor Contributes to Function of PACAP-27 (2010)
  • Author(s): Ushiyama, M., Ikeda, R., Yoshida, M., Mori, K., Kangawa, K., Sugawara, H., Inoue, K., Yamada, K., and Miyata, A.
  • Journal Title: Journal of Molecular Neuroscience Volume: 42 Pages: 341-348
  • Peer Reviewed
• [Journal Article] Gemcitabine and Paclitaxel Repress the Production of Vascular Endothelial Growth Factor Induced by Deferoxamine in Human Non-small Cell Lung Cancer A549cells (2010)
  • Author(s): Ikeda, R., Vermeulen, L. C., Jiang, Z., Lau, E. and Kolesar, J. M.
  • Journal Title: Experimental and Therapeutic Medicine Volume: 1 Pages: 853-857
  • Peer Reviewed
• [Journal Article] Establishment and Characterization of Irinotecan-resistant Human Non-small Cell Lung Cancer A549cells (2010)
  • Author(s): Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Pomplun, M. and Kolesar, J. M.
  • Journal Title: Molecular Medicine Reports Volume: 6 Pages: 1031-1034
  • Peer Reviewed
• [Journal Article] The role of thymidine phosphorylase in the induction of early growth response protein-1and thrombospondin-1by5-fluorouracil in human cancer carcinoma cells (2010)
  • Author(s): Matsushita, S., Ikeda, R., Nishizawa, Y., Che, X. F., Furukawa, T., Miyadera, K., Tabata, S., Ushiyama, M., Tajitsu, Y., Yamamoto, M., Takeda, Y., Minami, K., Mataki, H., Kanzaki, T., Yamada, K., Kanekura, T., Akiyama, S.
  • Journal Title: International Journal of Oncology Volume: 36 Pages: 1193-1200
  • Peer Reviewed
• [Journal Article] Major vault protein forms complexes with hypoxia-inducible factor(HIF)-1α and reduces HIF-1α level in ACHN human renal adenocarcinoma cells (2010)
  • Author(s): Iwashita, K., Ikeda, R., Takeda, Y., Sumizawa, T., Furukawa, T., Yamaguchi, T., Akiyama, S., Yamada K.
  • Journal Title: Cancer Science Volume: 101 Pages: 920-926
  • Peer Reviewed
• [Journal Article] Correlation between meropenem and doripenem use density and the incidence of carbapenem-resistant Pseudomonas aeruginosa (2009)
  • Author(s): Shigemi, A., Matsumoto, K., Yaji, K., Shimodozono, Y., Takeda, Y., Miyanohara, H., Kawamura, H., Orita, M., Tokuda, K., Nishi, J., Yamada, K.
  • Journal Title: International Journal of Antimicrobial Agents Volume: 34 Pages: 589-591
  • Peer Reviewed
• [Journal Article] Adverse effects of superselective intra-arterial infusion chemotherapy in patients with oral cancer (2009)
  • Author(s): Ushiyama, M., Ikeda, R., Yamaguchi, H., Miyawaki, A., Nitta, T., Yamaguchi, T., Matsumoto, K., Shimodouzono, Y., Furukawa, T., Akiyama, S., Nakamura N., Yamada, K.
  • Journal Title: Journal of Applied Therapeutic Research Volume: 7 Pages: 58-64
  • Peer Reviewed
• [Journal Article] Stability of hospital preparations of Azunol Water Gargles for pain relief in oral cancer patients with oral mucositis (2009)
  • Author(s): Ushiyama, M., Ikeda, R., Nitta, T., Tazitsu, Y., Miyawaki, A., Nishizawa, Y., Yamaguchi, T., Yamaguchi, H., Akatsuka, C., Shimodouzono, Y., Ushinohama, K., Sugawara, H., Sugihara, K., Nakamura, N., Takeda, Y., Yamada, K.
  • Journal Title: Cancer Therapy Volume: 7 Pages: 277-281
  • Peer Reviewed
• [Journal Article] Enhanced platelet responsiveness due to chilling and its relation to CD40ligand level and platelet-leukocyte aggregate formation (2009)
  • Author(s): Ayukawa, O., Nakamura, K., Kariyazono, H., Ikeda, R., Arima, J., Shinkawa, T., Iwase, H., Sakata, R., Yamada, K.
  • Journal Title: Blood Coagulation and Fibrinolysis Volume: 20 Pages: 176-184
  • Peer Reviewed
• [Presentation] Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells (2011)
  • Author(s): Ikeda, R., Tajitsu, Y., Nishizawa, Y., Tabata, S., Ushiyama, M., Furukawa, T., Akiyama, S., Yamada, K., Takeda., Y.
  • Organizer: 5^<th> Young Investigators Symposium on Clinical Pharmacetical Sciences
  • Place of Presentation: 名古屋大学医学部付属病院(名古屋市)
  • Year and Date: 2011-11-27
• [Presentation] チミジンホスホリラーゼ発現腫瘍での5-fluorouracil(5-FU)によるthrombospondin-1(TSP-1)発現誘導 (2011)
  • Author(s): 西澤由紀彦、池田龍二、田畑祥、田實裕介、俣木博徳、古川龍彦、牛山美奈、山口辰哉、山本雅達、松下茂人、秋山伸一、山田勝士、武田泰生
  • Organizer: 第64回日本薬理学会西南部会
  • Place of Presentation: KKRホテル博多(福岡市)
  • Year and Date: 2011-11-20
• [Presentation] 高浸透圧によるmajor vault protein(MVP)発現制御におけるSp1の役割 (2011)
  • Author(s): 田實裕介、池田龍二、田畑祥、西澤由紀彦、山口辰哉、牛山美奈、山本雅達、古川龍彦、秋山伸一、山田勝士、武田泰生
  • Organizer: 第64回日本薬理学会西南部会
  • Place of Presentation: KKRホテル博多(福岡市)
  • Year and Date: 2011-11-20
• [Presentation] 抗がん剤耐性機序の解明に向けて (2011)
  • Author(s): 池田龍二、武田泰生、山田勝士
  • Organizer: 第5回日本緩和医療薬学会年会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2011-09-24
• [Presentation] 現場の薬剤師が実践している研究活動と6年制薬学生への期待-抗がん剤耐性機序の解明に向けて- (2010)
  • Author(s): 池田龍二、武田泰生、牛山美奈、山口辰哉、下堂薗権洋、山田勝士
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学大学院医歯薬学総合研究科(長崎市)
  • Year and Date: 2010-12-12
• [Presentation] 5-fluor ouracilの血中濃度および遺伝子診断に基づいた投与量に関する検討 (2010)
  • Author(s): 新塘麻奈、松元一明、池田龍二、牛山美奈、横山雄太、武田泰生、石神純也、前村公成、有上貴明、夏越祥次、山田勝士
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学大学院医歯薬学総合研究科(長崎市)
  • Year and Date: 2010-12-11
• [Presentation] 抗がん薬耐性細胞におけるマイクロRNAの発現とその役割 (2010)
  • Author(s): 田口深雪、柴山良彦、池田龍二、武田泰生、山田勝士
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学大学院医歯薬学総合研究科(長崎市)
  • Year and Date: 2010-12-11
• [Presentation] 抗癌剤によって誘導されるmajor vault protein(MVP)の発現亢進機序の解明 (2010)
  • Author(s): 俣木博徳、池田龍二、田畑祥、田實裕介、西澤由紀彦、南謙太朗、山口辰哉、牛山美奈、山本雅達、武田泰生、秋山伸一、山田勝士
  • Organizer: 第63回日本薬理学会西南部会
  • Place of Presentation: 鹿児島県民交流センター(鹿児島市)
  • Year and Date: 2010-11-26
• [Presentation] ゲムシタビン耐性非小細胞肺がん細胞の耐性化機構 (2010)
  • Author(s): 池田龍二
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島市民文化ホール(鹿児島市)
  • Year and Date: 2010-09-26
• [Presentation] 抗がん薬耐性細胞におけるmiRNA126の発現とその役割 (2009)
  • Author(s): 田口深雪、柴山良彦、池田龍二、武田泰生、山田勝士
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 九州大学大学院薬学研究院(福岡市)
  • Year and Date: 2009-12-13
• [Presentation] Gemcitabine耐性細胞でのnucleoside transporterとribonucreotide reductaseの変化 (2009)
  • Author(s): 南謙太朗、古川龍彦、新里能成、車暁芳、山本雅達、池田龍二、武田泰生、秋山伸一、山田勝士
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 九州大学大学院薬学研究院(福岡市)
  • Year and Date: 2009-12-12
• [Presentation] チミジンホスホリラーゼ発現腫瘍での5-fluorouracil(5-FU)によるearly growth response factor-1(EGR-1)発現誘導 (2009)
  • Author(s): 西澤由紀彦、池田龍二、田實裕介、俣木博徳、武田泰生、古川龍彦、牛山美奈、山口辰哉、車暁芳、山本雅達、松下茂人、秋山伸一、山田勝士
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 九州大学大学院薬学研究院(福岡市)
  • Year and Date: 2009-12-12
• [Presentation] 神経接着分子コンタクチンを介した癌浸潤・転移のメカニズム (2009)
  • Author(s): 益田将吾、二川俊隆、西田健太朗、田畑祥、藤井寛樹、武田泰生、山田勝士
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: リジェール松山(松山市)
  • Year and Date: 2009-11-27
• [Presentation] 高浸透圧によって誘導されるmajor vault protein(MVP)の発現亢進機構の解明 (2009)
  • Author(s): 田實裕介、池田龍二、岩下健一、田畑祥、西澤由紀彦、山口辰哉、牛山美奈、山本雅達、車暁芳、古川龍彦、武田泰生、秋山伸一、山田勝士
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: リジェール松山(松山市)
  • Year and Date: 2009-11-27
• [Presentation] RNA-タンパク質複合体vaultはヒト腎癌由来細胞株ACHN細胞においてhypoxia-inducible factor-1α(HIF-1α)と結合し、そのユビキチン依存的な分解を促進する (2009)
  • Author(s): 岩下健一、池田龍二、武田泰生、住澤知之、古川龍彦、山口辰哉、秋山伸一、山田勝士
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: リジェール松山(松山市)
  • Year and Date: 2009-11-27
• [Presentation] チミジンホスホリラーゼによるNF-κBの活性化機構 (2009)
  • Author(s): 田畑祥、山本雅達、池田龍二、古川龍彦、車暁芳、新里能成、南謙太朗、向田直史、武田泰生、山田勝士、秋山伸一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-03