Molecular basis for resistance to anti-cancer agents by cancer microenvironment and development of novel molecular-targeted agents
Project/Area Number |
18K06788
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | University of Miyazaki |
Principal Investigator |
Ikeda Ryuji 宮崎大学, 医学部, 教授 (50398278)
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Project Period (FY) |
2018-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | がん微小環境 / がん幹細胞 / 抗がん薬耐性 / がん幹細胞モデル / インターロイキン32 / 抗がん剤耐性化 / シスプラチン耐性細胞 / MMP / Sphere形成 / トランスポーター / サイトカイン / S100A16 / がん分子標的薬 |
Outline of Final Research Achievements |
Cancer stem-like cells (CSCs), possessing self-renewal and multipotency capabilities, are widely recognized as the underlying cause of resistance to chemotherapy and radiotherapy within the tumor microenvironment. CSCs are known to exhibit a robust efflux system, expressing multiple adenosine triphosphate-binding cassette transporters, such as P-glycoprotein and breast cancer-resistant protein. Among the inflammatory cytokines implicated in cancer development, IL-32 was found to be overexpressed in CSCs. To investigate the effects of IL-32 on chemotherapy resistance, the cisplatin-resistant cell line, KCP-4, derived from human epidermoid carcinoma KB-3-1 cells was employed. Notably, the expression of IL-32 increased in KCP-4 cells compared to that in KB-3-1 cells. Employing small interfering RNA-mediated gene silencing techniques targeting IL-32 resulted in increased sensitivity to cisplatin, suggesting a crucial role for IL-32 in chemotherapy resistance and CSC formation.
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Academic Significance and Societal Importance of the Research Achievements |
腫瘍中には、自己複製能と多分化能を有するがん幹細胞の存在することが分かってきており、がん幹細胞の存在ががんの再発や薬剤抵抗性に寄与していることが想定される。がん幹細胞の特徴の1つとして、P-糖タンパク質(P-gp)やBCRP(breast cancer-resistant protein)といったABCトランスポーターが過剰発現している。悪性腫瘍に対する抗がん薬耐性は大きな問題であり、耐性・進展の機序を解明し、実用的な治療薬を開発することは重要且つ緊急課題であると考えられる。本研究では、今回、IL-32が抗がん薬耐性因子であることを示しており、今後の治療薬の開発に貴重な情報となり得る。
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Report
(6 results)
Research Products
(60 results)
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[Journal Article] Acteoside from Conandron ramondioides Reduces Microcystin-LR Cytotoxicity by Inhibiting Intracellular Uptake Mediated by OATP1B3.2023
Author(s)
Takumi S, Hashimoto K, Tomioka M, Sato M, He W, Komatsu Y, Aoki S, Ikeda R, Shiozaki K, Furukawa T, Komatsu M
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Journal Title
Planta Med.
Volume: 88
Issue: 06
Pages: 616-623
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ursodeoxycholic acid markedly promotes the absorption of microemulsion-formulated cyclosporine A: A case report2022
Author(s)
Takeshima, H., Yoshikawa, N., Akizuki, K., Hidaka, T., Shimoda, K., Ikeda, R.
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Journal Title
Journal of Clinical Pharmacy and Therapeutics
Volume: 47
Issue: 2
Pages: 260-262
DOI
Related Report
Peer Reviewed
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[Journal Article] The Cytokine Expression in Patients with Cardiac Complication after Immune Checkpoint Inhibitor Therapy2021
Author(s)
Tsuruda T, Yoshikawa N, Kai M, Yamaguchi M, Toida R, Kodama T, Kajihara K, Kawabata T, Nakamura T, Sakata K, Hatakeyama K, Gi T, Asada Y, Tono T, Kitamura K, Ikeda R.
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Journal Title
Internal Medicine
Volume: 60
Issue: 3
Pages: 423-429
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2021-02-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Delayed methotrexate elimination in a patient with primary central nervous system lymphoma: A case report2021
Author(s)
Urata, S., Yoshikawa, N, Saito, K., Tazaki, T., Ohno, R., Takeshima, H., Ikeda, R.
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Journal Title
Journal of Clinical Pharmacy and Therapeutics
Volume: 46
Issue: 6
Pages: 1796-1799
DOI
Related Report
Peer Reviewed
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[Journal Article] Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection2021
Author(s)
Yoshikawa,N., Yamada, A., Yokota, T., Yamada,Y., Kinoshita, M., Moritake, H., Ikeda, R.
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Journal Title
Cancers
Volume: 13
Issue: 18
Pages: 4643-4643
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Relationship between CYP3A5 Polymorphism and Tacrolimus Blood Concentration Changes in Allogeneic Hematopoietic Stem Cell Transplant Recipients during Continuous Infusion2021
Author(s)
Yoshikawa, N., Takeshima, H., Sekine, M., Akizuki, K., Hidaka, T., Shimoda, K., Ikeda, R.
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Journal Title
Pharmaceuticals
Volume: 14
Issue: 4
Pages: 353-353
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Anti-proliferative Activities of Some Bivalent Symmetrical 5-Substituted Hydantoin Derivatives towards Human Brain Glioma U251 Cells (U251) and Human Carcinoma Cells (KB3-1)2019
Author(s)
Furutachi M, Ota K, Fujisaki F, Ikeda R, Yoshikawa N, Yokota T, Takeda Y, Yokomizo K, Zhou JR, Kashige N, Miake F, Sumoto K
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 11
Pages: 1953-1956
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-11-01
Related Report
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[Journal Article] Anti-proliferative Activities towards Human Brain Glioma U251 Cells and Human Carcinoma Cells (KB3-1) of Some Twin-Drug Type Bivalent <i>C</i><sub>2</sub>-Symmetrical Phenylboronic Acid Derivatives2019
Author(s)
Furutachi M, Gondo T, Ikeda R, Yoshikawa N, Yokota T, Takeda Y, Yokomizo K, Zhou JR, Kashige N, Miake F, Sumoto K
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 5
Pages: 833-836
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-05-01
Related Report
Peer Reviewed
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[Journal Article] 5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase Promoter2019
Author(s)
Nishizawa Y, Ikeda R, Yamamoto M, Kawahara K, Shinsato Y, Minami K, Nitta M, Terazono H, Akiyama SI, Furukawa T, Takeda Y
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Journal Title
Anticancer Research
Volume: 39
Issue: 8
Pages: 4129-4136
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells2018
Author(s)
Tabata S, Yamamoto M, Goto H, Hirayama A, Ohishi M, Kuramoto T, Mitsuhashi A, Ikeda R, Haraguchi M, Kawahara K, Shinsato Y, Minami K, Saijo A, Toyoda Y, Hanibuchi M, Nishioka Y, Sone S, Esumi H, Tomita M, Soga T, Furukawa T, Akiyama SI.
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Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 6760-6760
DOI
NAID
Related Report
Peer Reviewed / Open Access
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