Fig. 4: Efficacy of iBAP-II in SCLC tumor growth and viability.

A The BAP1-dependency results in all SCLC cell lines were retrieved from the Cancer Dependency Map (DepMap). The left panel shows BAP1-dependency determined by genome-wide CRISPR screening. The right panel shows BAP1-dependency determined by genome-wide RNAi screening. B Four different SCLC cell lines NCI-H1963, NCI-H1882, NCI-H748, and KP3 (mouse) cells were treated with various concentrations of iBAP-II for 72 h. The cell number was determined by cell counting assay, n = 3. C Representative photographs show the colony formations in four different types of SCLC cells treated with either DMSO or iBAP-II for 72 h. D 5.0 × 10⁵ of mouse SCLC KP3 cells were inoculated into the right flank of nude mice. Two weeks after inoculation, vehicle (n = 5) or 50 mg/kg of iBAP-II (n = 5) was administered daily by intraperitoneal (IP) injections, and the tumor growth was measured every 4 days using a calibrated caliper. A two-tailed unpaired Student’s t-test was used for statistical analysis. **P < 0.01; *P < 0.05. E Images for representative tumor tissue from each mouse were taken at the end of the experiment. F, G GSEA analyses show the most enriched gene expression signatures correlated with downregulated genes in iBAP-II treated cells. H The mRNA levels of the MYC pathway genes BCL2, MAD2L1, C1QBP, GNL3, SNRPA, SRM, TFDP1, MCM7, and SYNCRIP were determined by real-time PCR in three different SCLC cells treated with either DMSO or iBAP-II for 24 h. I The graphic model shows the epigenetic balance between the BAP1 and ncPRC1 complexes in determining ASCL1 gene expression and ASCL1-dependent transcriptional signatures in SCLC.