AM80 INCREASES CHEMOSENSITIVITY TO DOXORUBICIN IN A HUMAN NEUROBLASTOMA SK-N-BE2 CELLS VIA DOWNREGULATION OF MRP1 EXPRESSION BY TARGETING MYCN GENE

JIANYONG WANG*, HONGLIANG SUN**, XINXINYU***, XIAOLI WANG*, LI WANG*, JIANYING LIU* AND AIMIN LI*,#

* Department of Pediatrics, Yantai Yu Huang Ding Hospital Affiliated to Qingdao University Medical College, Yantai, Shandong, China, 264000 - **Department of Surgery, Yantai Yu Huang Ding Hospital Affiliated to Qingdao University Medical College, Yantai, Shandong, China, 264000 - ***Department of Pediatrics, Binzhou People's Hospital, Binzhou, Shandong, China, 256603

Objective: To investigate the effect of Tamibarotene (Am80), a retinoic acid derivative, on the growth of human neuroblastoma SK-N-BE2 cells. Crucially, to study the ability of Am80 to sensitize SK-N-BE2 cells toward doxorubicin, which is commonly used for the treatment of neuroblastoma, was assessed.

Methods: Cell viability was examined by the Cell Counting Kit-8 (CCK-8) assay. The uptake and efflux of 5(6)-carboxyfluorescein diacetate (CFDA) and the accumulation of doxorubicin assays was detected using a flow cytometer (FACS). The mRNA expression levels were detected via Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of proteins was examined by western blotting.

Results: Am80 significantly inhibited cell growth in a dose-dependent manner and reduced the IC50 value of doxorubicin in SK-N-BE2 cells. Simultaneously, Am80 could increase intracellular drug accumulation. Furthermore, Am80 decreased the expression of Multidrug resistance-associated protein 1 (MRP1) at both mRNA and protein levels. Deeper experiments elucidated that Am80 could suppress MRP1 expression through downregulating the expression level of MYCN.

Conclusion: Taken together, these results suggest that Am80 as new and potent agent has wide therapeutic and/or adjuvant applications for neuroblastoma chemotherapy.