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Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells.
- Source :
-
BMC complementary medicine and therapies [BMC Complement Med Ther] 2020 Mar 14; Vol. 20 (1), pp. 84. Date of Electronic Publication: 2020 Mar 14. - Publication Year :
- 2020
-
Abstract
- Background: Current chemotherapies for Burkitt lymphoma (BL) have dramatically improved its clinical outcome. However, chemoresistance can lead to chemotherapy failure and very poor prognosis; thus, novel strategies are urgently required for patients with drug-resistant BL. To investigate the mechanisms underlying drug resistance in BL, we established drug-resistant BL cell lines: HS-Sultan/ADM (adriamycin-resistant), HS-Sultan/VCR (vincristine-resistant), HS-Sultan/DEX (dexamethasone-resistant), and HS-Sultan/L-PAM (melphalan-resistant).<br />Methods: Drug transporter and survival factor expression were investigated the using western blotting and real time polymerase chain reaction. Cell survival was analyzed by trypan blue dye exclusion method.<br />Results: The established cell lines acquired cross-resistance to adriamycin, vincristine, dexamethasone, and melphalan and exhibited 50% inhibitory concentration values 106-, 40-, 81-, and 45-fold higher than the parental cell lines, respectively. We found that protein and mRNA expression of MDR1 and Survivin were higher in drug-resistant BL cells than in the parent cells. Treatment with verapamil, an MDR1 inhibitor, or Survivin siRNA alongside each anti-cancer drug suppressed the proliferation of all drug-resistant BL cells. Src kinase activity was higher in all resistant cell lines than the parental cells; suppressing Src with dasatinib restored drug sensitivity by reducing MDR1 and Survivin expression.<br />Conclusions: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.
Details
- Language :
- English
- ISSN :
- 2662-7671
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC complementary medicine and therapies
- Publication Type :
- Academic Journal
- Accession number :
- 32171300
- Full Text :
- https://doi.org/10.1186/s12906-020-2879-8