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MicroRNA‐mediated suppression of P‐glycoprotein by quantum dots in lung cancer cells
Author(s) -
Sun Yimin,
Zhang Jie,
Yin Huancai,
Yin Jian
Publication year - 2020
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3924
Subject(s) - microrna , p glycoprotein , a549 cell , lung cancer , multiple drug resistance , cancer research , gene , chemistry , cancer cell , downregulation and upregulation , microbiology and biotechnology , biology , cancer , medicine , biochemistry , cell , genetics , antibiotics
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 Cd 2+ 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.