中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 9
Sep.  2024
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(9): 1853-1858

Construction of pancreatic cancer organoids and their sensitivity to chemotherapy drugs

DOI: 10.12449/JCH240921
  • 1.

    School of Public Health，Inner Mongolia Medical University，Hohhot 010110，China

  • 2.

    Department of Biochemistry，Institute of Basic Medical Sciences，Chinese Academy of Medical Sciences，Beijing 100005，China

  • 3.

    Department of Pancreatogastric Surgery，Cancer Hospital，Chinese Academy of Medical Sciences，Beijing 100124，China

Research funding:

Inner Mongolia Autonomous Region Health Science and Technology Program Fund (202201227);

Project of Inner Mongolia Medical University (YKD2021MS001)

More Information
  • Corresponding author: ZHANG Xingguang， zxg311@126.com （ORCID： 0000-0002-3295-0890）
  • Received Date: 2024-02-26
  • Accepted Date: 2024-04-15
  • Published Date: 2024-09-25
    Abstract
  •   Objective  To construct and identify a patient-derived organoid model， and to investigate the sensitivity of chemotherapy drugs using this model.  Methods  Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion， and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture. Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved. The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations； Cell Titer-Glo®3D reagent was used to measure cell viability， and the results of drug sensitivity were analyzed.  Results  Two patient-derived pancreatic cancer organoids were successfully constructed， and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient. Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil， and patient 1 was more sensitive than patient 2. There were individual differences in the response to drugs between the organoids from different patients.  Conclusion  The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test， which is expected to provide a reference for clinical medication.

     

    • FullText(HTML)
  • loading
    • References(24)
  • [1]
    BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68( 6): 394- 424. DOI: 10.3322/caac.21492.
    [2]
    ZHU B, WU XM, GUO TY, et al. Epidemiological characteristics of pancreatic cancer in China from 1990 to 2019[J]. Cancer Control, 2021, 28: 10732748211051536. DOI: 10.1177/10732748211051536.
    [3]
    GORAL V. Pancreatic cancer: Pathogenesis and diagnosis[J]. Asian Pac J Cancer Prev, 2015, 16( 14): 5619- 5624. DOI: 10.7314/apjcp.2015.16.14.5619.
    [4]
    ZHANG LL, SANAGAPALLI S, STOITA A. Challenges in diagnosis of pancreatic cancer[J]. World J Gastroenterol, 2018, 24(‍‍ 19): 2047- 2060. DOI: 10.3748/wjg.v24.i19.2047.
    [5]
    LIU KD, GENG YD, WANG LZ, et al. Systematic exploration of the underlying mechanism of gemcitabine resistance in pancreatic adenocarcinoma[J]. Mol Oncol, 2022, 16(‍ 16): 3034- 3051. DOI: 10.1002/1878-0261.13279.
    [6]
    SYED AR, CARLETON NM, HORNE Z, et al. Survival trends for resectable pancreatic cancer using a multidisciplinary conference: The impact of post-operative chemotherapy[J]. J Gastrointest Cancer, 2020, 51( 3): 836- 843. DOI: 10.1007/s12029-019-00303-z.
    [7]
    WU S, REN JQ, WU HX, et al. Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer[J]. Chin J Dig Surg, 2023, 22( 5): 616- 622. DOI: 10.3760/cma.j.cn115610-20230323-00125.

    武帅, 任加强, 吴含雪, 等. 胰腺癌根治性切除术后吉西他滨化疗方案耐药因素分析[J]. 中华消化外科杂志, 2023, 22( 5): 616- 622. DOI: 10.3760/cma.j.cn115610-20230323-00125.
    [8]
    ILIC M, ILIC I. Epidemiology of pancreatic cancer[J]. World J Gastroenterol, 2016, 22( 44): 9694- 9705. DOI: 10.3748/wjg.v22.i44.9694.
    [9]
    SATO T, VRIES RG, SNIPPERT HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche[J]. Nature, 2009, 459( 7244): 262- 265. DOI: 10.1038/nature07935.
    [10]
    SATO T, STANGE DE, FERRANTE M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium[J]. Gastroenterology, 2011, 141( 5): 1762- 1772. DOI: 10.1053/j.gastro.2011.07.050.
    [11]
    BARKER N, HUCH M, KUJALA P, et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro[J]. Cell Stem Cell, 2010, 6( 1): 25- 36. DOI: 10.1016/j.stem.2009.11.013.
    [12]
    BARTFELD S, BAYRAM T, VAN DE WETERING M, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection[J]. Gastroenterology, 2015, 148( 1): 126- 136. e 6. DOI: 10.1053/j.gastro.2014.09.042.
    [13]
    HUCH M, GEHART H, VAN BOXTEL R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver[J]. Cell, 2015, 160( 1-2): 299- 312. DOI: 10.1016/j.cell.2014.11.050.
    [14]
    General Office of National Health Commission. Standard for diagnosis and treatment of pancreatic cancer(2022 edition)[J]. J Clin Hepatol, 2022, 38( 5): 1006- 1030. DOI: 10.3969/j.issn.1001-5256.2022.05.007.

    国家卫生健康委办公厅. 胰腺癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38( 5): 1006- 1030. DOI: 10.3969/j.issn.1001-5256.2022.05.007.
    [15]
    ZHAO B. Application prospects of organoids in organ transplantation[J]. Organ Transplantation, 2022, 13( 2): 169- 175. DOI: 10.3969/j.issn.1674-7445.2022.02.004.

    赵冰. 类器官在器官移植领域的应用前景[J]. 器官移植, 2022, 13( 2): 169- 175. DOI: 10.3969/j.issn.1674-7445.2022.02.004.
    [16]
    SI WXR, JIANG M. Application of organoids in basic research and clinical translation of cancers[J]. Tianjin Med J, 2024, 52( 1): 28- 32. DOI: 10.11958/20231475.

    司吴雪蓉, 蒋明. 类器官在癌症基础研究和临床转化中的应用[J]. 天津医药, 2024, 52( 1): 28- 32. DOI: 10.11958/20231475.
    [17]
    SUN GC, LI HY, CHEN J, et al. Research progress and application of organoid in biomedicine[J]. Clin J Med Off, 2023, 51( 11): 1206- 1210. DOI: 10.16680/j.1671-3826.2023.11.28.

    孙广晨, 李宏宇, 陈江, 等. 类器官在生物医学中研究进展及应用[J]. 临床军医杂志, 2023, 51( 11): 1206- 1210. DOI: 10.16680/j.1671-3826.2023.11.28.
    [18]
    DEMYAN L, HABOWSKI AN, PLENKER D, et al. Pancreatic cancer patient-derived organoids can predict response to neoadjuvant chemotherapy[J]. Ann Surg, 2022, 276( 3): 450- 462. DOI: 10.1097/SLA.0000000000005558.
    [19]
    BOJ SF, HWANG CI, BAKER LA, et al. Organoid models of human and mouse ductal pancreatic cancer[J]. Cell, 2015, 160( 1-2): 324- 338. DOI: 10.1016/j.cell.2014.12.021.
    [20]
    HUCH M, BONFANTI P, BOJ SF, et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis[J]. EMBO J, 2013, 32( 20): 2708- 2721. DOI: 10.1038/emboj.2013.204.
    [21]
    NEAL JT, LI XN, ZHU JJ, et al. Organoid modeling of the tumor immune microenvironment[J]. Cell, 2018, 175( 7): 1972- 1988. e 16. DOI: 10.1016/j.cell.2018.11.021.
    [22]
    SCHUTH S, BLANC SL, KRIEGER TG, et al. Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system[J]. J Exp Clin Cancer Res, 2022, 41( 1): 312. DOI: 10.1186/s13046-022-02519-7.
    [23]
    CATTANEO CM, DIJKSTRA KK, FANCHI LF, et al. Tumor organoid-T-cell coculture systems[J]. Nat Protoc, 2020, 15( 1): 15- 39. DOI: 10.1038/s41596-019-0232-9.
    [24]
    ZHANG J, TAVAKOLI H, MA L, et al. Immunotherapy discovery on tumor organoid-on-a-chip platforms that recapitulate the tumor microenvironment[J]. Adv Drug Deliv Rev, 2022, 187: 114365. DOI: 10.1016/j.addr.2022.114365.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (142) PDF downloads(25) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return