Multi-drug-resistance efflux in cisplatin-naive and cisplatin-exposed A2780 ovarian cancer cells responds differently to cell culture dimensionality
| Autor: | Geoffrey Liu, Mariana Bleker de Oliveira, Sergey N. Krylov, Laurie Ailles, Vasilij Koshkin, Chun Peng, Allan Covens |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cisplatin
Cancer Research cell clusters Chemistry cytometry of reaction rate constant Cell intrinsic multi-drug resistance Articles Cell cycle circulating tumor cells multi-cellular spheroids medicine.anatomical_structure Circulating tumor cell ovarian cancer Oncology Cell culture Apoptosis single cells medicine Cancer research acquired multi-drug resistance cell monolayer Efflux Cytometry medicine.drug |
| Zdroj: | Molecular and Clinical Oncology |
| ISSN: | 2049-9469 2049-9450 |
| Popis: | A primary reason for chemotherapy failure is chemoresistance, which is driven by various mechanisms. Multi-drug resistance (MDR) is one such mechanism that is responsible for drug extrusion from the intracellular space. MDR can be intrinsic and thus, may pre-exist the first application of chemotherapy. However, MDR may also be acquired during tumor exposure to chemotherapeutic agents. To understand whether cell clustering can influence intrinsic and acquired MDR, the present study assessed cultured monolayers (representing individual cells) and spheroids (representing clusters) formed by cisplatin-naive (intrinsic MDR) and cisplatin-exposed (acquired MDR) lines of ovarian cancer A2780 cells by determining the cytometry of reaction rate constant (CRRC). MDR efflux was characterized using accurate and robust cell number vs. MDR efflux rate constant (k MDR) histograms. Both cisplatin-naive and cisplatin-exposed monolayer cells presented unimodal histograms; the histogram of cisplatin-exposed cells was shifted towards a higher k MDR value suggesting greater MDR activity. Spheroids of cisplatin-naive cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of cisplatin-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of cisplatin-exposed cells but with a moderate shift towards greater MDR activity. A flow-cytometry assessment of multidrug resistance-associated protein 1 transporter levels in monolayers and dissociated spheroids revealed distributions similar to those of k MDR, thus, suggesting a plausible molecular mechanism for the observed differences in MDR activity. The observed greater effect of cell clustering on intrinsic rather than in acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells. |
| Databáze: | OpenAIRE |
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