J Cancer 2019; 10(22):5483-5493. doi:10.7150/jca.34506

Research Paper

A Novel Resveratrol-Arsenic Trioxide Combination Treatment Synergistically Induces Apoptosis of Adriamycin-Selected Drug-Resistant Leukemia K562 Cells

Jing Chen1*, Baoying Tian2*, Cunmin Zhou1, Jingjing Sun1, Li Lin1, Shucheng Jin1, Quanrui Liu1, Siyu Fu1, Lian Liu1, Hang Liu1, Zhewen Zhang1, Caili Li3, Hulai Wei1✉

1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, 730000
2. Hanzhong vocational and technical college, Hanzhong, Shanxi, 723000
3. School of Medicine of Northwest University for Nationalities, Lanzhou, Gansu 730030, P.R. China
* Contributed equally

Abstract

Leukemia cells can develop resistance to apoptosis induced by chemotherapeutic agents. Concomitant multidrug resistance of cells remains the greatest clinical obstacle in the effective treatment of blood and solid tumors. Natural products have been identified that possess the capacity to modulate chemotherapeutic resistance and induce apopotosis. In this study, we generated adriamycin-resistant K562 leukemia (K562/RA) cells and compared the responses of sensitive and resistant leukemia cells to the natural products arsenic trioxide (ATO) and resveratrol (Rsv), with a view to determining whether Rsv potentiates the sensitivity of drug-resistant cells to ATO-induced apoptosis and the associated molecular mechanisms. Our results showed that resistance of K562/RA cells induced by adriamycin treatment was significantly higher (115.81-fold) than that of parental K562 cells. Simultaneously, K562/RA cells were cross-resistant to multiple agents, with the exception of ATO. Rsv enhanced the sensitivity of K562/RA cells to ATO and reduced the required dose of ATO as well as associated adverse reactions by promoting the proliferation inhibitory and apoptosis-inducing effects of ATO, which may be associated with reduced expression of the drug resistance genes mdr1/P-gp, mrp1/MRP1 and bcrp/BCRP, as well as the apoptotic inhibitory genes bcl-2, NF-κB and P53, and conversely, activation of caspase-3. Our collective findings indicate that ATO and Rsv synergistically enhance the sensitivity of drug-resistant leukemia cells to apoptosis.

Keywords: leukemia, multidrug resistance, arsenic trioxide, resveratrol, apoptosis

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Chen J, Tian B, Zhou C, Sun J, Lin L, Jin S, Liu Q, Fu S, Liu L, Liu H, Zhang Z, Li C, Wei H. A Novel Resveratrol-Arsenic Trioxide Combination Treatment Synergistically Induces Apoptosis of Adriamycin-Selected Drug-Resistant Leukemia K562 Cells. J Cancer 2019; 10(22):5483-5493. doi:10.7150/jca.34506. Available from http://www.jcancer.org/v10p5483.htm