Product Description

Doxorubicin is a cytotoxic, broad-spectrum anthracycline antibiotic commonly used as an anticancer chemotherapeutic agent. It exhibits intrinsic fluorescence and inhibits DNA replication by suppressing topoisomerase II. Additionally, doxorubicin downregulates basal phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase, while inducing both apoptosis and autophagy. Notably, it also inhibits human DNA topoisomerase I.

Screeningbio‘s K562/Doxorubicin  resistance cell line generated by exposing to increasing concentration of drug for certain period of time. After stable acquire resistance, cells were harvested and characterized for drug resistance by 7 days proliferation assay.

Data

Target Background

Doxorubicin (Adriamycin) is a potent anthracycline chemotherapeutic agent that intercalates into DNA, inhibits topoisomerase II, and generates reactive oxygen species (ROS), thereby inducing DNA double-strand breaks, oxidative stress, and apoptosis in rapidly dividing cancer cells. However, the acquisition of drug resistance significantly limits its long-term efficacy in malignancies such as breast cancer, sarcomas, and lymphomas.

Mechanistically, doxorubicin resistance arises through multiple cellular adaptations. Overexpression of ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (MDR1/ABCB1), reduces intracellular drug accumulation, while alterations in topoisomerase IIβ expression or activity diminish drug targets. Enhanced DNA repair capacity via pathways such as nucleotide excision repair (NER) and homologous recombination (HR), along with upregulation of anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL) or loss of p53 function, confers survival advantages. Additionally, activation of NF-κB and PI3K/Akt signaling promotes chemoresistance, and elevated levels of intracellular glutathione (GSH) or antioxidant enzymes such as superoxide dismutase (SOD) and catalase counteract ROS-mediated damage.

Understanding these mechanisms is critical for designing strategies to overcome resistance, such as co-administration of efflux pump inhibitors (e.g., verapamil, valspodar), targeting redox adaptation pathways, inhibiting anti-apoptotic Bcl-2 family proteins (e.g., using venetoclax), or employing patient-derived resistant cell models to inform personalized combination regimens.