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. 2021 Mar 22;3(1):zcab010. doi: 10.1093/narcan/zcab010

Figure 6.

Figure 6.

The TRDMT1 Inhibitor YW-1842 specifically sensitizes cells to DNA damage agents. (A) A screening scheme of YW-1842. (B) SCE WT cells were transfected with TA-KR and were cultured with 2.5 μM/l compound YW-1842 or not for 6 h, m5C (n = 3, 50 cells per replicated, mean ± SD) was stained and quantified. (CandD) DR-GFP (C) or EJ5-GFP (D) cells were pre-treated with 2.5 μM/l compound YW-1842 for 6 h or TRDMT1 siRNA for 48 h, or DMSO. Then, the cells were transfected with NLS-I-SceI plasmid to induce DSB. The efficiency of HR (C) or NHEJ (D) was analyzed by flow-cytometry (n = 3, mean ± SD). (E) After seeding, MCF-7, HCC1954 and HCC1937 cells were pre-treated with or without 2.5 μM/l compound YW-1842 for 6 h, then cultured with chemotherapy drugs (1 μM/l cisplatin; 1 μM/l ATRi AZ20; 10 μM/l ATMi KU55933; 1 μM/l PARPi Olaparib) for 10 days. The survival rate of these cells was analyzed (n = 3, mean ± SD). (F) TRDMT1 KO U2OS cells were transfected with GFP-TRDMT1WT or GFP-TRDMT1G155V with or without 2.5 μM/l compound YW-1842, the survival rate of these cells after IR or cisplatin was shown (n = 3, mean ± SD).