Background:
Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant
cells appear, treatment becomes difficult, and the prognosis is poor.
Objective:
In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and
identified the genes involved in cisplatin resistance.
Methods:
Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant
cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6-
overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin-
resistant cells were generated, and the sensitivity of cisplatin was examined.
Results:
The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but
the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin
resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that
the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity
was partially suppressed in UBE2L6-silenced cells.
Conclusion:
These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute
to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a
molecular target that overcomes cisplatin resistance.
