Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening

Griner, Lesley Mathews; Gampa, Kalyani; Do, Toan; Nguyen, Huyen; Farley, David R.; Hogan, Christopher; Auld, Douglas S.; Silver, Serena J.

doi:10.3791/57476-v

Cited by 2 publications

(1 citation statement)

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“…1 ). Conventionally, drug efficacy assays are performed by culturing the cells under 3D conditions only at the drug screening step using cells initially subcultured under 2D conditions [ [13] , [14] , [15] ]. This approach cannot be defined as truly 3D cell culture-based drug screening, because cancer cells lose their unique in vivo characteristics from the early 2D subculture stage and the expression of tumor-related proteins targeted by the anticancer drugs is altered.…”

Section: Introductionmentioning

confidence: 99%

3D cell subculturing pillar dish for pharmacogenetic analysis and high-throughput screening

Lee,

Hwang,

Song

et al. 2023

Materials Today Bio

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Section: Introductionmentioning

confidence: 99%

3D cell subculturing pillar dish for pharmacogenetic analysis and high-throughput screening

Lee,

Hwang,

Song

et al. 2023

Materials Today Bio

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Hypoxia represses early responses of prostate and renal cancer cells to YM155 independent of HIF-1α and HIF-2α

Danielpour

Corum²,

Welford

et al. 2022

Current Research in Pharmacology and Drug Discovery

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The imidazolium compound Sepantronium Bromide (YM155) successfully promotes tumor regression in various pre-clinical models but has shown modest responses in human clinical trials. We provide evidence to support that the hypoxic milieu of tumors may limit the clinical usefulness of YM155. Hypoxia (1% O 2 ) strongly (>16-fold) represses the cytotoxic activity of YM155 on prostate and renal cancer cells in vitro . Hypoxia also represses all early signaling responses associated with YM155, including activation of AMPK and retinoblastoma protein (Rb), inactivation of the mechanistic target of rapamycin complex 1 (mTORC1), inhibition of phospho-ribosomal protein S6 (rS6), and suppression of the expression of Cyclin Ds, Mcl-1 and Survivin. Cells pre-incubated with hypoxia for 24 h are desensitized to YM155 even when they are treated with YM155 under atmospheric oxygen conditions, supporting that cells at least temporarily retain hypoxia-induced resistance to YM155. We tested the role of hypoxia-inducible factor (HIF)-1α and HIF-2α in the hypoxia-induced resistance to YM155 by comparing responses of YM155 in VHL-proficient versus VHL-deficient RCC4 and 786-O renal cancer cells and silencing HIF expression in PC-3 prostate cancer cells. Those studies suggested that hypoxia-induced resistance to YM155 occurs independent of HIF-1α and HIF-2α. Moreover, the hypoxia mimetics deferoxamine and dimethyloxalylglycine, which robustly induce HIF-1α levels in PC-3 cells under atmospheric oxygen, did not diminish their early cellular responses to YM155. Collectively, our data support that hypoxia induces resistance of cells to YM155 through a HIF-1α and HIF-2α-independent mechanism. We hypothesize that a hypothetical hypoxia-inducer factor (HIF-X) represses early signaling responses to YM155.

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Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening

Cited by 2 publications

References 0 publications

3D cell subculturing pillar dish for pharmacogenetic analysis and high-throughput screening

3D cell subculturing pillar dish for pharmacogenetic analysis and high-throughput screening

Hypoxia represses early responses of prostate and renal cancer cells to YM155 independent of HIF-1α and HIF-2α

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