Journal: bioRxiv
Article Title: The SF3B1 inhibitor pladienolide B massively inhibits DNA damage signaling and repair and counteracts resistance to platinum salts in Non-Small Cell Lung Cancer
doi: 10.64898/2026.02.17.706284
Figure Lengend Snippet: (a) Cell viability assay in cells treated or not for 72 hours with increasing concentrations of pladienolide B (nM). Mean ± SD. n = 3. (b) Quantification of apoptosis (%) by flow cytometry in cells treated with 5 nM pladienolide B for indicated times. Mean ± SD. n = 3. (c) Clonogenic assay in H460S/R cells treated or not for 14 days with 1 nM pladienolide B or 1 µM cisplatin. Lower panel: number of colonies with number in untreated condition being arbitrarily assigned to 100% survival. Mean ± SD. n = 3. (d) Spheroids from H460S/R cells treated with complete medium and DMSO as control, or 0.5 nM or 1 nM pladienolide B for the indicated days. Upper panels: representative images of spheroids at day 14. Lower panel: spheroids area (µm 2 ). Mean ± SD. n = 5 spheroids/condition. A representative experiment of 3 independent ones. (e) Representative immunoblots of SF3B1 in H460S/R or A549S/R cells. GAPDH was used as a loading control. n = 3. (f) H460R or A549R cells were transfected for 72 hours with a control siRNA or two distinct siRNA targeting Sf3b1 mRNA as indicated. Left panels: representative immunoblots of SF3B1. GAPDH was used as a loading control. Right panels: quantification of apoptosis (%). Mean ± SD. n = 3. (a, b, c, d, f) Unpaired t test. * p< 0.05, ** p< 0.01, *** p< 0.001, **** p< 0.0001, ns: not significant. (g) Overall Rate Response (ORR) at Day 20 for all NSCLC PDXs treated or not (control) with 2.5 mg/kg or 5 mg/kg pladienolide B (ip, Day 1-Day 4-Day 8-Day 11). Two-tails Mann-Whitney t test. ** p< 0.01. (h) Probability of progression (Relative Tumor Volume = 2) in control and pladienolide B-treated PDXs. n = 7 (LCIM1 is not included). Log-rank t test. ** p < 0.01.
Article Snippet: Human Non-Small Cell Lung Carcinoma (NSCLC) cell lines (H460, A549, H1299, H2170, H3255, H460, PC9, CALU-1, H1975, H226, H358, HCC827) were authenticated by DNA STR profiling (ATCC cell line Authentification Service, LGC standards, Molsheim, France) and routinely tested for mycoplasma contamination.
Techniques: Viability Assay, Flow Cytometry, Clonogenic Assay, Control, Western Blot, Transfection, MANN-WHITNEY