Study on the radiation/heat/anti-cancer drag sensitivity enhanced by siRNA in mutated-p53 cancer cells

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Nara Medical University
• Principal Investigator: OHNISHI Ken Nara Medical University, 保健医療学部, 教授 (50152195)
• Co-Investigator(Kenkyū-buntansha): HATANO Osamu (40164850)
• Project Period (FY): 2008 – 2010
• Keywords: p53 / 増感 / RNA干渉 / siRNA / シグナル伝達因子 / AKT

Research Abstract

The aim of this study is to examine the mechanism that contributes to radio-sensitization by NBS1-siRNA or XIAP-siRNA observed more effectively in human lung cancer cells having mutated p53 than in those having wild-type p53. This study showed that (1) p53 associates with AKT intracellularly and (2) AKT inhibitors (Wortmannin, LY294002) enhances radio-sensitivity in both of wild-type p53 and mutated p53 cells. From these results it was suggested that the association between p53 and AKT is a cause of the predominant radio-sensitization observed mutated p53 cells.

Research Products

• [Journal Article] Induction of multinucleation in oral squamous cell carcinoma tissue with mutated p53 surviving boron neutron capture therapy. (2011)
  • Author(s): Fujita Y, Yamamoto N, Kato I, Iwai S, Ono K, Sakurai Y, Ohnishi K, Ohnishi T, Yura Y.
  • Journal Title: International Journal of Radiation Biology. 87 Pages: 293-301
  • Peer Reviewed
• [Journal Article] Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage. (2011)
  • Author(s): Noda T, Takahashi A, Kondo N, Mori E, Okamoto N, Nakagawa Y, Ohnishi K, Zdzienicka, MZ, Thompson LH, Helleday T, Asada H, Ohnishi T.
  • Journal Title: Biochemical and Biophysical Research Communications 404 Pages: 206-210
  • Peer Reviewed
• [Journal Article] Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. (2010)
  • Author(s): Nagata Y, Takahashi A, Ohnishi K, Ota I, Ohnishi T, Tojo T, Taniguchi S.
  • Journal Title: International Journal of Oncology. 37 Pages: 1001-1010
  • Peer Reviewed
• [Journal Article] DNA ligase IV is a potential molecular target in ACNU sensitivity. (2010)
  • Author(s): Kondo N, Takahashi A, Mori E, Noda T, Su X, Ohnishi K, McKinnon P, Sakaki T, Nakase H, Ono K, Ohnishi T.
  • Journal Title: Cancer Sci. 101 Pages: 1881-1885
  • Peer Reviewed
• [Journal Article] ATM is the predominant kinase involved in the phosphorylation of histone H2AX after heating. (2010)
  • Author(s): Takahashi A, Mori E, Su X, Nakagawa Y, Okamoto N, Uemura H, Kondo N, Noda T, Toki A, Ejima Y, Chen JD, Ohnishi K, Ohnishi T.
  • Journal Title: J Radiat Res (Tokyo). 51 Pages: 417-422
  • Peer Reviewed
• [Journal Article] Biphasic effects of nitric oxide radicals on radiation-induced lethality and chromosome aberrations in human lung cancer cells carrying different p53 gene status. (2010)
  • Author(s): Su X, Takahashi A, Guo G, Mori E, Okamoto N, Ohnishi K, Iwasaki T, Ohnishi T.
  • Journal Title: Int J Radiat Oncol Biol Phys. 77 Pages: 559-565
  • Peer Reviewed
• [Journal Article] Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors : its independency of p53 status. (2010)
  • Author(s): Masunaga S, Tano K, Nakamura J, Watanabe M, Kashino G, Takahashi A, Tanaka H, Suzuki M, Ohnishi K, Kinashi Y, Liu Y, Ohnishi T, Ono K.
  • Journal Title: J Radiat Res 51 Pages: 27-35
  • Peer Reviewed
• [Journal Article] Effective new cancer therapies which are independent of p53 gene status. (2010)
  • Author(s): Takahashi A, Ohnishi K, Kondo K, Mori E, Noda T, Ohnishi T.
  • Journal Title: J Nara Med Assoc 61 Pages: 19-33
  • Peer Reviewed
• [Journal Article] Downregulation of SIK2 expression promotes the melanogenic program in mice. (2010)
  • Author(s): Horike N, Kumagai A, Shimono Y, Onishi T, Itoh Y, Sasaki T, Kitagawa K, Hatano O, Takagi H, Susumu T, Teraoka H, Kusano KI, Nagaoka Y, Kawahara H, Takemori H.
  • Journal Title: Pigment Cell Melanoma Res 23 Pages: 809-819
  • Peer Reviewed
• [Journal Article] SIK2 is a new key regulator for neuronal survival after ischemia via TORC1-CREB. (2010)
  • Author(s): Sasaki T, Takemori H, Yagita Y, Terasaki Y, Uebi T, Horike N, Takagi H, Susumu T, Teraoka H, Kusano K, Hatano O, Oyama N, Sugiyama Y, Sakoda S, Kitagawa K.
  • Journal Title: Neuron in press
  • Peer Reviewed
• [Journal Article] Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma. (2009)
  • Author(s): Fujita Y, Kato I, Iwai S, Ono K, Suzuki M, Sakurai Y, Ohnishi K, Ohnishi T, Yura Y
  • Journal Title: Radiat Oncol電子ジャーナル 4,No.63
  • Peer Reviewed
• [Journal Article] DNA ligase IV as a new molecular target for temozolomide (2009)
  • Author(s): Kondo N, Takahashi A, Mori E, Ohnishi K, McKinnon PJ, Sakaki T, Nakase H, Ohnishi T
  • Journal Title: Biochem Biophys Res Commun 387 Pages: 656-660
  • Peer Reviewed
• [Journal Article] Expression of aromatase CYP19 and its relationship with parameters in NSCLC. (2009)
  • Author(s): Oyama T, Kagawa N, Sugio K, Uramoto H, Hatano O, Harada N, Kaneko K, Kawamoto T, Yasumoto K.
  • Journal Title: Front Biosci 14 Pages: 2285-2292
  • Peer Reviewed
• [Journal Article] The spatial and temporal expression of delta-like protein 1 in the rat pituitary gland during development. (2009)
  • Author(s): Nakakura T, Sato M, Suzuki M, Hatano O, Takemori H, Taniguchi Y, Minoshima Y, Tanaka S.
  • Journal Title: Histochem Cell Biol 131 Pages: 141-153
  • Peer Reviewed
• [Journal Article] DNA damage recognition proteins localize along heavy ion induced tracks in the cell nucleus (2008)
  • Author(s): Takahashi A, Yamakawa N, Kirita T, Omori K, Ishioka N, Furusawa Y, Mori E, Ohnishi K, Ohnishi T
  • Journal Title: J Radiat Res 49 Pages: 645-652
  • Peer Reviewed
• [Journal Article] Protein microarray analysis of apoptosis-related protein expression following heat shock in human tongue squamous cell carcinomas containing different p53 phenotypes (2008)
  • Author(s): Kajihara A, Takahashi A, Ohnishi K, Imai Y, Yamakawa N, Yasumoto J, Ohnishi T, Kirita T
  • Journal Title: Int J Hyperthermia 24 Pages: 605-612
  • Peer Reviewed
• [Journal Article] Heat induces H2AX foci formation in mammalian cells (2008)
  • Author(s): Takahashi A, Mori E, Somakos GI, Ohnishi K, Ohnishi T
  • Journal Title: Mutat Res/Genet Toxicol and Environ Mutagen 656 Pages: 88-92
  • Peer Reviewed
• [Journal Article] Effective enhancement of X-ray-induced apoptosis in human cancer cells with mutated p53 by siRNA targeting XIAP (2008)
  • Author(s): Ohnishi K, Nagata Y, Takahashi A, Taniguchi S, Ohnishi T
  • Journal Title: Oncol Rep 20 Pages: 57-61
  • Peer Reviewed
• [Journal Article] High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation (2008)
  • Author(s): Yamakawa N, Takahashi A, Mori E, Imai Y, Furusawa Y, Ohnishi K, Kirita T, Ohnishi T
  • Journal Title: Cancer Sci 99 Pages: 1455-1460
  • Peer Reviewed
• [Journal Article] Development of thermotolerance requires interaction between polymerase-beta and heat shock proteins (2008)
  • Author(s): Takahashi A, Yamakawa N, Mori E, Ohnishi K, Yokota S, Sugo N, Aratani Y, Koyama H, Ohnishi T
  • Journal Title: Cancer Sci 99 Pages: 973-978
  • Peer Reviewed
• [Journal Article] Time course and spacial distribution of UV effects on human skin in organ culture (2008)
  • Author(s): Mori E, Takahashi A, Kitagawa K, Kakei S, Tsujinaka D, Unno M, Nishikawa S, Ohnishi K, Hatoko M, Murata N, Watanabe M, Furusawa Y, Ohnishi T
  • Journal Title: J Radiat Res 49 Pages: 269-277
  • Peer Reviewed
• [Journal Article] p53 targeting can enhance cancer therapy via radiation, heat and anti-cancer agents (2008)
  • Author(s): Ohnishi T, Takahashi A, Mori E, Ohnishi K
  • Journal Title: Anticancer Agents Med Chem 8 Pages: 564-570
  • Peer Reviewed
• [Journal Article] ER stress is the initial response to polyglutamine toxicity in PC12 cells. (2008)
  • Author(s): Nakayama H, Hamada M, Fujikake N, Nagai Y, Zhao J, Hatano O, Shimoke K, Isosaki M, Yoshizumi M, Ikeuchi T.
  • Journal Title: Biochem Biophys Res Commun 377 Pages: 550-555
  • Peer Reviewed
• [Journal Article] siRNA Targeted for NBS1 enhances heat sensitivity in human anaplastic thyroid carcinoma cells.
  • Author(s): Okamoto N, Takahaski A, Ota I, Ohnishi K, Mori E, Kondo N, Noda T, Nakagawa Y, Uemura H, Yane K, Hosoi H, Ohnishi T.
  • Journal Title: International Journal of Hyperthermia in press
  • Peer Reviewed
• [Presentation] 放射線増感作用を示す植物生理活性物質、特にフラボノイドの分子標的放射線増感剤としての有用性 (2011)
  • Author(s): 大西健
  • Organizer: 第13回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 20110000
• [Presentation] Hsp90阻害剤Celastrolのヒト腫瘍細胞の放射線増感 (2011)
  • Author(s): 瀬川達矢
  • Organizer: 第13回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 20110000
• [Presentation] DNA修復を標的としたアルキル化剤の増感効果 (2010)
  • Author(s): 近藤夏子
  • Organizer: 第12回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 20100000
• [Presentation] ヒト甲状腺未分化がん細胞におけるDNA修復遺伝子NBS1を標的としたsiRNAによる温熱増感効果(第2報)-NBS1siRNAとDSBの指標であるγH2AXとの関連について- (2010)
  • Author(s): 岡本倫朋
  • Organizer: 第12回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 20100000
• [Presentation] Cell cycle effects on radioadaptation or radioenhancement of cell survival and chromosomal aberrations choreographed by NO radicals. (2010)
  • Author(s): Su X
  • Organizer: 12^<th> Symposium on Sensitization of Cancer Treatment in Nara.
  • Place of Presentation: Nara
  • Year and Date: 20100000
• [Presentation] siRNA targeted for NBS1 enhances heat sensitivity in human anaplastic thyroid carcinoma cells. (2010)
  • Author(s): 岡本倫朋
  • Organizer: The 5^<th> Asian Congress of Hyperthermic Oncology (ACHO) & The 27^<th> Japanese Congress of Thermal Medicine (JCTM).
  • Place of Presentation: Fukuoka
  • Year and Date: 20100000
• [Presentation] ホルムアルデヒド誘導DNA損傷はFANCD1, DとGを介したHRによって修復される (2010)
  • Author(s): 野田太一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100000
• [Presentation] ヒト甲状腺未分化がんにおけるNBS1標的siRNAの温熱増感効果 (2010)
  • Author(s): 岡本倫朋
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100000
• [Presentation] 抗がん作用を持つフラボノイド類のスクリーニング (2010)
  • Author(s): 大西健
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 20100000
• [Presentation] NO radicals choreograph p53-different radio-sensitivity in human lung cancer cells. (2009)
  • Author(s): Su X
  • Organizer: 2nd Asian Congr Radiat Res.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090000
• [Presentation] Protein microarray analysis of apoptosis-related protein expression following heat shock in human toungue squamous cell carcinomas containing different p53 phenotypes. (2009)
  • Author(s): Kajihara A
  • Organizer: 2nd Asian Congr Radiat Res.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090000
• [Presentation] The therapeutic target of DNA repair pathways against alkylating agents. (2009)
  • Author(s): Kondo N
  • Organizer: 2nd Asian Congr Radiat Res.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090000
• [Presentation] Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity in lung cancer cells bearing different p53 gene status. (2009)
  • Author(s): Nagata Y
  • Organizer: 2nd Asian Congr Radiat Res.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090000
• [Presentation] Formaldehyde-induced DNA damage and its repair. (2009)
  • Author(s): 野田太一
  • Organizer: 2nd Asian Congr Radiat Res.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090000
• [Presentation] Rapamycin inhibits proliferation and enhances cisplatin-induced apoptosis in human head and neck cancer cells. (2009)
  • Author(s): Ota I
  • Organizer: 2nd Asian Congr Radiat Res.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090000
• [Presentation] がん細胞の生と死の制御 (2009)
  • Author(s): 高橋昭久
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 20090000
• [Presentation] Fanconi anemia経路を標的としたアルキル化剤の増感効果 (2009)
  • Author(s): 近藤夏子
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 20090000
• [Presentation] ATM dominantly phosphorylate histone H2AX after heat treatment. (2009)
  • Author(s): 高橋昭久
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20090000
• [Presentation] Identification of a new molecular target of alkylating agents, TMZ and fotemustine. (2009)
  • Author(s): Kondo N
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20090000
• [Presentation] あらかじめの温熱前処理による放射線および温熱抵抗性の獲得 (2009)
  • Author(s): 高橋昭久
  • Organizer: 第48回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 富山
  • Year and Date: 20090000
• [Presentation] Biphasic effects of NO radicals on radiation-induced cell lethality and chromosome aberrations in H1299/wtp53 cells. (2009)
  • Author(s): Su X
  • Organizer: 第15回癌治療増感研究会
  • Place of Presentation: 京都
  • Year and Date: 20090000
• [Presentation] DNA二本鎖切断修復を標的としてアルキル化剤TMZの増感効果 (2009)
  • Author(s): 近藤夏子
  • Organizer: 第15回癌治療増感研究会
  • Place of Presentation: 京都
  • Year and Date: 20090000
• [Presentation] p53遺伝子型の異なる肺がん細胞におけるAkt/mTORシグナル抑制による増殖抑制効果 (2009)
  • Author(s): 長田陽子
  • Organizer: 第15回癌治療増感研究会
  • Place of Presentation: 京都
  • Year and Date: 20090000
• [Presentation] 分子シャペロンp53C末端ペプチドと放射線併用による変異型p53腫瘍の増殖遅延 (2008)
  • Author(s): 大西健
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
  • Year and Date: 20080000
• [Presentation] 哺乳細胞における温熱誘導γH2AXフォーカス形成 (2008)
  • Author(s): 高橋昭久
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20080000
• [Presentation] 哺乳細胞における温熱誘導γH2AXフォーカス形成 (2008)
  • Author(s): 高橋昭久
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 20080000
• [Presentation] 温熱によるヒストンH2AXリン酸化機構の解明 (2008)
  • Author(s): 高橋昭久
  • Organizer: 日本ハイパーサーミア学会第25回大会
  • Place of Presentation: 名古屋市
  • Year and Date: 20080000
• [Presentation] 界面活性剤Tween80と温熱の併用処理による細胞増殖抑制のメカニズム (2008)
  • Author(s): 大西健
  • Organizer: 第47回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 高知市
  • Year and Date: 20080000
• [Presentation] 低線量放射線前照射による温熱抵抗性の獲得 (2008)
  • Author(s): 高橋昭久
  • Organizer: 第47回日本医学放射線学会生物部会学術大会
  • Place of Presentation: 高知市
  • Year and Date: 20080000
• [Presentation] p53C末端ペプチドと放射線併用による変異型p53保有移植腫瘍の増殖抑制 (2008)
  • Author(s): 大西健
  • Organizer: 第14回癌治療増感研究会
  • Place of Presentation: 鈴鹿市
  • Year and Date: 20080000
• [Presentation] Tween80 enhances heat-induced arrest of cell proliferation through regulating Akt and NBS1 signaling pathways. (2008)
  • Author(s): Ohnishi K
  • Organizer: 10th Int Congr Hyperthermic Oncol.
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080000
• [Presentation] The study of target genes deciding heat-sensitivity. (2008)
  • Author(s): 高橋昭久
  • Organizer: 10^<th> International Congress on Hyperthermic Oncology.
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080000
• [Presentation] Localization of DSB-recognizing proteins in the nucleus after heat treatment. (2008)
  • Author(s): Ohnishi T
  • Organizer: 10^<th> International Congress on Hyperthermic Oncology.
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080000
• [Presentation] Tween80 enhances heat-induced arrest of cell proliferation through regulating AKT and NBS1 signaling pathways. (2008)
  • Author(s): Ohnishi K
  • Organizer: 10^<th> International Congress on Hyperthermic Oncology.
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080000
• [Presentation] Development of thermotolerance requires interaction between polymerase β and heat shock proteins. (2008)
  • Author(s): Mori E
  • Organizer: 10^<th> International Congress on Hyperthermic Oncology.
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080000
• [Presentation] Molecular chaperon therapy against human cancer cells. (2008)
  • Author(s): Ohnishi T
  • Organizer: 4th Int Congr Stress Resp Biol Med.
  • Year and Date: 20080000
• [Book] 毎日健康サロン、がん温熱療法ガイドブック (2008)
  • Author(s): 大西健, 分著
  • Total Pages: 130-131
• [Book] がんの温熱免疫療法 (2008)
  • Author(s): 大西健, 分著
  • Total Pages: 6-9
  • Publisher: 診断と治療社