Ying Xie, Xu Yan, Ling Sun
Department of Blood Transfusion, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland)
Med Sci Monit 2019; 25:2542-2552
In clinical practice, many patients become multidrug resistant during chemotherapy, resulting in reduced or no healing effect. Therefore, the present study focused on bufalin, which is extracted from a traditional Chinese medicine named Chan Su (Venenum bufonis). We assessed the effect of bufalin in reversing K562/A02 cell drug resistance and inducing apoptosis, and explored the possible mechanism by which bufalin induces K562/A02 cell apoptosis.
MATERIAL AND METHODS: We used flow cytometry to evaluate intracellular ADM concentration, and RT-PCR and Western blot analysis were used to assess the effect of nuclear factor erythroid-2-related factor 2 (Nrf2) bufalin-related resistance gene expression. We used MTT and flow cytometry to detect apoptosis, and RT-PCR and Western blot were used to detect endoplasmic reticulum stress and apoptosis gene action.
RESULTS: We found that bufalin can increase the concentration of Adriamycin (ADM) in K562/A02 cells by inhibiting the expression of Nrf2 and related drug resistance factors. The results showed that bufalin induced apoptosis of K562/A02 cells by the IRE1alpha/TRAF2/JNK/caspase-12 pathway.
CONCLUSIONS: These results suggest bufalin can reverse drug resistance in K562/A02 cells and that it induces apoptosis of K562/A02 cells by the IRE1alpha/TRAF2/JNK/caspase-12 pathway.
Keywords: Drug Resistance, Multiple, Endoplasmic reticulum stress, K562 Cells, Medicine, Chinese Traditional