Multi-drug-resistance efflux in cisplatin-naive and cisplatin-exposed a2780 ovarian cancer cells responds differently to cell culture dimensionality

Abstract

A primary reason for chemotherapy failure is chemo-resistance, 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 chemo-therapy. 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-naïve (intrinsic MDR) and cisplatin-exposed (acquired MDR) lines of ovarian cancer A2780 cells by deter-mining the cytometry of reaction rate constant (CRRC). MDR efflux was characterized using accurate and robust cell number vs. MDR efflux rate constant (kMDR) histograms. Both cispl-atin-naïve and cisplatin-exposed monolayer cells presented unimodal histograms; the histogram of cisplatin-exposed cells was shifted towards a higher kMDR value suggesting greater MDR activity. Spheroids of cisplatin-naïve cells presented a bimodal histogram indicating the presence of two subpopula-tions with different MDR activity. In contrast, spheroids of.