MicroRNA‐mediated suppression of P‐glycoprotein by quantum dots in lung cancer cells

Abstract

The interactions between adenosine triphosphate‐binding cassette (ABC) transporters and nano‐sized materials are attracting increasing attention, due to their great potential in overcoming the multidrug resistance (MDR) phenomena in cancer treatment. However, the inner mechanisms involved in the interactions are largely unknown. In this study, two commercial quantum dots (QDs), CdSe/ZnS‐MPA and CdSe/ZnS‐GSH, were tested for their interactions with P‐glycoprotein (P‐gp), as well as the relating mechanisms in lung cancer (A549) cells. Both QDs significantly suppressed the gene and protein expressions of P‐gp in A549 cells. To explain this, the gene expressions of nine relating microRNAs (miRNAs) were evaluated. The results indicated a shared up‐regulation of miR‐34b and miR‐185 by both QDs. Furthermore, mimics and inhibitors of miR‐34b and miR‐185 significantly enhanced and suppressed the gene and protein expressions of P‐gp, respectively, confirming the modulatory function of these two miRNAs on P‐gp. Interestingly, expressions of both miRNAs were suppressed during treatment with Cd2+ and doxorubicin, which induced the expression of P‐gp, indicating the universality of these miRNAs‐related mechanisms. Thus, as miR‐34b and miR‐185 participated in the suppression of P‐gp functions in A549 cells they could be interesting targets for the treatment of lung cancer.

Bioactive Compounds of Raspberry Oil Emulsions Induced Oxidative Stress via Stimulating the Accumulation of Reactive Oxygen Species and NO in Cancer Cells

“…The results of the calculated correlations may suggest that raspberry oil emulsions affect the NO-dependent mechanism of DNA strand damage in LoVo and MCF7 cells for both doxorubicin-resistant and sensitive lines. This is especially important when the exocytosis of drugs is reduced either by lysosomal or P-glycoprotein action [ 44 , 45 ]. In the next stage of the research, it is planned to investigate the effect of the studied oils in combination with doxorubicin on cell cultures—evaluating the impact of reducing drug exocytosis and increasing the effectiveness of chemotherapy.…”

Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer

“…Furthermore, QDs and carbon-based nanomaterials have been employed to conjugate drugs, antibodies and adjuvants to enhance anticancer therapeutic efficacy [ 137 , 138 ]. In one study, P-gp-miR-34b and P-gp-miR-185 conjugated with CdSe/ZnS-MPA QDs and CdSe/ZnS-GSH QDs significantly inhibited P-gp expression in lung cancer A549 cells [ 139 ]. Graphene-based QDs (GQDs) have also been evaluated for their ability to modulate P-gp-mediated MDR.…”

Applications and Immunological Effects of Quantum Dots on Respiratory System

“…In this context, Sun et al reported that CdSe/ZnS-3mercaptopropionic acid and CdSe/ZnS-glutathione QDs could inhibit the expressions of P-glycoprotein gene and protein accounting for multidrug resistance of lung cancer cells by inducing miR-185 and miR-34b, indicating miR-185 and miR-34b could be also interesting and potential targets for lung cancer treatment (34). Moreover, Green Synthesis Derived CdS QDs with Camellia sinensis leaf extracts arrested lung tumor cells cycle and decreased cell viability (35). In addition they showed that leaf extract-mediated CdS QDs inhibited pulmonary infection-related gram positive Streptococcus pyogens and gram negative Serratia marcescens in vitro (36).…”