Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids

被引:34
|
作者
Azharuddin, Mohammad [1 ]
Roberg, Karin [1 ,2 ]
Dhara, Ashis Kumar [3 ]
Jain, Mayur Vilas [4 ]
Darcy, Padraig [5 ]
Hinkula, Jorma [1 ]
Slater, Nigel K. H. [6 ]
Patra, Hirak K. [1 ,6 ]
机构
[1] Linkoping Univ, Dept Clin & Expt Med IKE, Linkoping, Sweden
[2] Reg Ostergotland, Anaesthet Operat & Specialty Surg Ctr, Dept Otorhinolaryngol Linkoping, Ostergotland, Sweden
[3] Natl Inst Technol Durgapur, Dept Elect Engn, Durgapur, India
[4] Lund Univ, Div Mol Med & Gene Therapy, Lund, Sweden
[5] Linkoping Univ, Div Drug Res LAFO, Dept Med & Hlth Sci IMH, Linkoping, Sweden
[6] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge, England
基金
欧盟地平线“2020”;
关键词
OVERCOMING RESISTANCE; OVARIAN-CANCER; EXPRESSION; CARCINOMA; MECHANISMS; DOCETAXEL; TRANSPORTERS; CHEMOTHERAPY; PROTEIN; TISSUE;
D O I
10.1038/s41598-019-56273-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.
引用
收藏
页数:12
相关论文
共 50 条
  • [1] Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
    Mohammad Azharuddin
    Karin Roberg
    Ashis Kumar Dhara
    Mayur Vilas Jain
    Padraig Darcy
    Jorma Hinkula
    Nigel K. H. Slater
    Hirak K. Patra
    Scientific Reports, 9
  • [2] Evaluation of Taxol(R) in head and neck squamous carcinoma multicellular tumor spheroids
    GriffonEtienne, G
    Merlin, JL
    Marchal, C
    ANTI-CANCER DRUGS, 1997, 8 (01) : 48 - 55
  • [3] GROWTH OF BREAST-CANCER CELLS AS MULTICELLULAR TUMOR SPHEROIDS
    YUHAS, JM
    TARLETON, AE
    MOLZEN, KB
    BRYSK, MM
    LI, AP
    IN VITRO-JOURNAL OF THE TISSUE CULTURE ASSOCIATION, 1978, 14 (04): : 360 - 361
  • [4] Differential thermo-resistance of multicellular tumor spheroids
    Khoei, S
    Goliaei, B
    Neshasteh-Riz, A
    IRANIAN JOURNAL OF SCIENCE AND TECHNOLOGY, 2004, 28 (A1): : 107 - 116
  • [5] Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence
    Aramini, Beatrice
    Masciale, Valentina
    Grisendi, Giulia
    Bertolini, Federica
    Maur, Michela
    Guaitoli, Giorgia
    Chrystel, Isca
    Morandi, Uliano
    Stella, Franco
    Dominici, Massimo
    Haider, Khawaja Husnain
    CANCERS, 2022, 14 (04)
  • [6] Multicellular tumor spheroids of LNCaP-Luc prostate cancer cells as in vitro screening models for cytotoxic drug
    Jouberton, Elodie
    Voissiere, Aurelien
    Penault-Llorca, Frederique
    Cachin, Florent
    Miot-Noirault, Elisabeth
    AMERICAN JOURNAL OF CANCER RESEARCH, 2022, 12 (03): : 1116 - 1128
  • [7] 3D Multicellular Tumor Spheroids in a Microfluidic Droplet System for Investigation of Drug Resistance
    Lee, Sang Ik
    Choi, Yoon Young
    Kang, Seong Goo
    Kim, Tae Hyeon
    Choi, Ji Wook
    Kim, Young Jae
    Kim, Tae-Hyung
    Kang, Taewook
    Chung, Bong Geun
    POLYMERS, 2022, 14 (18)
  • [8] High-Throughput Drug Screening of Multicellular Tumor Spheroids
    Pardo, Ana Maria P.
    Gitschier, Hannah J.
    Randle, David H.
    Riss, Terry
    AMERICAN LABORATORY, 2016, 48 (08) : 8 - 11
  • [9] EFFECTS OF CISPLATIN PLUS FLUOROURACIL VS CISPLATIN PLUS CYTARABINE ON HEAD AND NECK SQUAMOUS MULTICELLULAR TUMOR SPHEROIDS
    KOHNO, N
    OHNUMA, T
    BILLER, HF
    HOLLAND, JF
    ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 1988, 114 (02) : 157 - 161
  • [10] ISOLATION OF QUIESCENT CELLS FROM MULTICELLULAR TUMOR SPHEROIDS USING CENTRIFUGAL ELUTRIATION
    BAUER, KD
    KENG, PC
    SUTHERLAND, RM
    CANCER RESEARCH, 1982, 42 (01) : 72 - 78