D-501036 is a promising anti-cancer compound that exhibits potent anti-proliferative activity against various types of human cancers through the induction of double strand DNA breaks. To determine drug resistance mechanism related to this class of DNA-damaging agents, a KB-derived D-501036-resistant cell line (S4) was established. Results showed that S4 cells exhibit enhanced DNA rejoining ability as compare to KB cells, through up-regulation of the non-homologous end joining activity. In conclusion, enhancement of NHEJ activity plays important role in the development of D-501036-resistance and targeting NHEJ-related molecules maybe able to overcome drug resistance to DNA damaging agents.
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