Multidrug-resistant P-glycoprotein assembly revealed by Tariquidar-probe’s super-resolution imaging
2021
As an efflux pump, P-glycoproteins (P-gps) are over-expressed in many cancer cell types to confer them multi-drug resistance. Many studies have focused on elucidating its molecular structure or protein expression; however, the relationship between molecular assembly and dysfunction remains unclear. Super-resolution microscope is an excellent imaging tool to reveal the molecular biological details, but its high-quality imaging often suffers from the labeling method currently available. Here, by exploiting its specificity and small size, Tariquidar (specific inhibitor of P-gp) is modified by TAMRA to form the small chemical probe of P-gp. By direct stochastic optical reconstruction microscopy (dSTORM) imaging, Tariquidar-TAMRA was firstly reveal to own a higher labeling superiority and high binding specificity. Then, with application of Tariquidar-TAMRA labeling, we found that P-gps are accumulate into larger and denser clusters on cancer cells and drug-sensitive cells than on normal cells and drug-sensitive cells, indicating that P-gp can facilitate pumping efficiency by aggregating together to form function platforms. Moreover, these specific distribution patterns might serve as potential biomarkers for tumor and drug therapy screening.
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