TY - JOUR
T1 - Graphene Quantum Dots Downregulate Multiple Multidrug-Resistant Genes via Interacting with Their C-Rich Promoters
AU - Luo, Chao
AU - Li, Yanfang
AU - Guo, Lijuan
AU - Zhang, Fangwei
AU - Liu, Hui
AU - Zhang, Jiali
AU - Zheng, Jing
AU - Zhang, Jingyan
AU - Guo, Shouwu
N1 - Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/11/8
Y1 - 2017/11/8
N2 - Multidrug resistance (MDR) is the major factor in the failure of many forms of chemotherapy, mostly due to the increased efflux of anticancer drugs that mediated by ATP-binding cassette (ABC) transporters. Therefore, inhibiting ABC transporters is one of effective methods of overcoming MDR. However, high enrichment of ABC transporters in cells and their broad substrate spectra made to circumvent MDR are almost insurmountable by a single specific ABC transporter inhibitor. Here, this study demonstrates that graphene quantum dots (GQDs) could downregulate the expressions of P-glycoprotein, multidrug resistance protein MRP1, and breast cancer resistance protein genes via interacting with C-rich regions of their promoters. This is the first example that a single reagent could suppress multiple MDR genes, suggesting that it will be possible to target multiple ABC transporters simultaneously with a single reagent. The inhibitory ability of the GQDs to these drug-resistant genes is validated further by reversing the doxorubicin resistance of MCF-7/ADR cells. Notably, GQDs have superb chemical and physical properties, unique structure, low toxicity, and high biocompatibility; hence, their capability of inhibiting multiple drug-resistant genes holds great potential in cancer therapy.
AB - Multidrug resistance (MDR) is the major factor in the failure of many forms of chemotherapy, mostly due to the increased efflux of anticancer drugs that mediated by ATP-binding cassette (ABC) transporters. Therefore, inhibiting ABC transporters is one of effective methods of overcoming MDR. However, high enrichment of ABC transporters in cells and their broad substrate spectra made to circumvent MDR are almost insurmountable by a single specific ABC transporter inhibitor. Here, this study demonstrates that graphene quantum dots (GQDs) could downregulate the expressions of P-glycoprotein, multidrug resistance protein MRP1, and breast cancer resistance protein genes via interacting with C-rich regions of their promoters. This is the first example that a single reagent could suppress multiple MDR genes, suggesting that it will be possible to target multiple ABC transporters simultaneously with a single reagent. The inhibitory ability of the GQDs to these drug-resistant genes is validated further by reversing the doxorubicin resistance of MCF-7/ADR cells. Notably, GQDs have superb chemical and physical properties, unique structure, low toxicity, and high biocompatibility; hence, their capability of inhibiting multiple drug-resistant genes holds great potential in cancer therapy.
KW - ABC transporters
KW - gene regulation
KW - graphene quantum dots
KW - multidrug resistance
UR - http://www.scopus.com/inward/record.url?scp=85026371486&partnerID=8YFLogxK
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U2 - 10.1002/adhm.201700328
DO - 10.1002/adhm.201700328
M3 - Article
C2 - 28748603
AN - SCOPUS:85026371486
SN - 2192-2640
VL - 6
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 21
M1 - 1700328
ER -