Figure 2 from Targeting PRMT1 Reduces Cancer Persistence and Tumor Relapse in EGFR- and KRAS-Mutant Lung Cancer
Year: 2025
Type: other
Abstract: PRMT1 knockdown decreases persistence in STAT1-high EGFRmut and KRASG12C lung cancer cell lines. A and B, Cells were treated with type I PRMT inhibitors (PRMTi) at 0.1 or 1 μmol/L, with (A) or without (B) targeted drugs. For EGFRmut cells, the targeted drug was 100 nmol/L osimertinib, and for KRASG12C cells, the targeted drug was 1-μmol/L sotorasib. The pan-type I PRMT inhibitor GSK3368715 (GSK715), PRMT3-selective inhibitor SGC707, and PRMT4-selective inhibitor TP-064 were used. Persister fitness was calculated by normalizing cell viability after a six-day combination treatment to viability with targeted drug alone (A). General cancer cell fitness was calculated by normalizing cell viability after a three-day treatment with PRMTi alone to no PRMTi control (B). The graphs show the mean ± standard deviation (n = 3). C, Engineered lung cancer cells expressing PRMT1-targeting shRNA (shPRMT1) were treated with or without targeted drugs: 100 nmol/L osimertinib (Osi) for HCC827 shPRMT1 and 1-μmol/L sotorasib (Soto) for H1373 and H358 shPRMT1 cells. Doxycycline (Dox, 100 ng/mL) was administered concurrently with targeted drugs to ensure PRMT1 knockdown. Treatments lasted for at least 1 week before being discontinued to allow the regrowth of persister cells. The treatment schedules are indicated by gray triangles. Cells were continuously monitored using phase contrast live cell imaging. Cell confluence per well is reported as mean ± standard deviation, with three to five replicate wells per condition. Statistical comparisons between groups were based on the integrated confluence over time (area under curve; AUC), using one-sided Mann–Whitney tests. The significance of the results is indicated by symbols: *, P ≤ 0.05; **, P ≤ 0.01; ****, P ≤ 0.0001.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4406630821