In this study, we have explored the possibility of the combination of the high reactivity of nano Fe3O4 or Au nanoparticles and daunomycin, one of the most important antitumor drugs in the treatment of acute leukemia clinically, to inhibit MDR of K562/A02 cells. Initially, to determine whether the magnetic nanoparticle Fe3O4 and Au can facilitate the anticancer drug to reverse the resistance of cancer cells, we have explored the cytotoxic effect of daunomycin (DNR) with and without the magnetic nano-Fe3O4 or nano-Au on K562 and K562/A02 cells by MTT assay. Besides, the intracellular DNR concentration and apoptosis of the K562/A02 cells was further investigated by flow cytometry and confocal fluorescence microscopic studies. The MDR1 gene expression of the K562/A02 cells was also studied by RT-PCR method. Our results indicate that 5.0 x 10(-7) M nano-Fe3O4 or 2.0 x 10(-8) M nano-Au is biocompatible and can apparently raise the intracellular DNR accumulation of the K562/A02 cells and increase the apoptosis of tumor cells. Moreover, our observations illustrate that although these two kinds of nanoparticles themselves could not lower the MDRI gene expression of the K562/A02 cells, yet they could degrade the MDR1 gene level when combining with anticancer drug DNR. This raises the possibility to combine the nano-Fe3O4 or nano-Au with DNR to reverse the drug resistance of K562/A02 cells, which could offer a new strategy for the promising efficient chemotherapy of the leukemia patients.
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Eur J Med Chem
December 2024
School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China. Electronic address:
P-glycoprotein (P-gp)-caused multidrug resistance (MDR) is a crucial factor in the cancer chemotherapy failure. Herein, a total of twenty two azo-containing WK-X-34 (WK34, a third generation P-gp inhibitor) derivatives were synthesized as novel P-gp inhibitors. Biological evaluation revealed that compound 7i effectively reversed P-gp-mediated MDR in K562/A02 cells, with a higher reversal fold (RF) value than WK34 (142.
View Article and Find Full Text PDFEur J Pharmacol
November 2024
The State Key Laboratory of Basis and New Drug Development of Natural and Nuclear Drugs, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 100193, Beijing, China. Electronic address:
Compound 5p is a 4β-N-substituted podophyllotoxin derivative, which exhibited potent activity toward drug-resistant K562/A02 cells and decreased MDR-1 mRNA expression. Here, we further investigated its detail mechanism and tested its antitumor activity. 5p exerted catalytic inhibition of topoisomerase IIα, and didn't show the inhibitor of topoisomerase I.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
April 2024
General Department, General Hospital of Central Theater Command of the Chinese People's Liberation Army, Wuhan 430070, Hubei Province, China.E-mail:
Objective: To study the effect of arctigenin(ARG) on adriamycin(ADM) resistance of leukemia cell line K562/A02 and the underlying mechanism.
Methods: Human leukemia cell line K562 and ADM-resistant cell line K562/A02 were cultured and treated with 2.5-50 µmol/L ADM.
Zhongguo Shi Yan Xue Ye Xue Za Zhi
June 2023
Department of Hematology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.E-mail:
Objective: To detect the differential expressions of miR-451, and in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of and , and the mechanism of miR-451 involved in drug resistance in leukemia.
Methods: CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells.
Eur J Med Chem
March 2023
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China. Electronic address:
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp) is a main barrier to the success of cancer chemotherapies. In this study, fourteen novel dibenzoazepine-tetrahydroisoquinoline hybrids were prepared as potential P-gp inhibitors to surmount MDR caused by P-gp. Amongst them, 8a displayed the most potent inhibition effect on P-gp, thus effectively reversing P-gp-mediated drug resistance with a reversal fold (RF) value of 93.
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