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[SDF-1α/CXCR4 Mediated Drug Resistance Can be Reversed by Ibrutinib in Acute Lymphoblastic Leukemia]
Yuan-Yuan Hu1, Shan-Dong Tao1, Jing-Jing Ma1
1Department of Hematology, Huai'an First People's Hospital Affiliaed to Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Objective:
To explore the effect of Ibrutinib on the chemoresistance mediated by SDF-1α/CXCR4 axis in ALL cells.
Methods:
Flow cytometry was used to detect the apoptosis of cell line and expression of surface membrane CXCR4, Western blot was used to determine the expression level of CXCR4, ERK and Bcl-xL proteins, qPCR was used to assay the mRNA level of CXCR4.
Results:
Ibrutinib enhanced the apoptosis induced by adriamycin(ADR) (17.100±4.3% to 28.133±3.16%); Ibrutinib inhibited the phosphorylation of CXCR4 induced by SDF-1α and with concentration- and time- dependent manner (r24h=-0.99659, r48h=-0.99764, r=-0.99980). Ibrutinib inhibited the expression and activity of CXCR4 downstream signaling molecules pERK and BCL-xL.
Conclusion:
Ibrutinib can enhance the sensitivity of SUP-B15 to ADR, reverse SDF-1α/CXCR4-mediated chemoresistance in Ph+ acute lymphoblastic leukemia cells. This mechanism of ibrutinib may be assosiated with inhibiting CXCR4/ERK/BCL-xL.
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