human sclc cell lines h446  (ATCC)

Journal: Nature Communications

Article Title: Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy

doi: 10.1038/s41467-026-71608-4

Figure Lengend Snippet: A Left panel: The expression of 15 ACB genes for each SCLC ( n = 50) and NSCLC cell lines ( n = 98). Right panel: EC 50 values of selected SCLC ( n = 13) and NSCLC ( n = 32) cell lines. Dots represent mean EC 50 values derived from two (H1105, HCC33, HCC15, H1573, H1792, H1437, H3122, and H1651) or at least three independent experiments for the remaining cell lines, each performed with biological triplicates. Statistical significance was assessed using a two-tailed unpaired t- test. The exact p values are indicated in the figure. Cell lines with known loss-of-function mutations in KEAP1 or Cul3 are indicated as black dots. B The heatmap with the protein levels of SLC7A11, GSR, and TXN, analyzed in total cell extracts by immunoblotting. Cell lines with loss-of-function mutations (LOF) in KEAP1 or Cul3 are indicated with asterix. Protein expression in H1944 was set to 1 for each protein and for each experiment. Relative data represent mean of two (SLC7A11, GSR, TXN1 in SCLC; SLC7A11 in NSCLC) or three (GSR and TXN1 in NSCLC) independent experiments. C Expression values of ACB genes were normalized to normal lung tissue. Box plots display the median (center line), interquartile range (box), and whiskers extending to 1.5× the interquartile range; individual data points are overlaid. Statistical differences among groups were assessed using the Kruskal–Wallis test followed by two-sided Dunn’s multiple comparisons test comparing each tumor type with SCLC. Exact p values are indicated in the figure when significant (<0.05). Sample sizes for each group are indicated on the x -axis labels. D , E Data are presented as mean of EC 50 values of three independent experiments, each performed in biological replicate. E Statistical significance was assessed using a two-tailed unpaired t -test. Exac t p values are indicated in the figure when significant (<0.05). D CN: derived from chemo-naïve patients, PC: derived from patients after cisplatin plus etoposide therapy. E H69 CPR , H526 CPR , H209 CPR are cisplatin-resistant sublines. Source data are provided as a file.

Article Snippet: Human SCLC suspension cell lines (ATCC: NCI-H69 HTB-119, NCI-H82 HTB-175, NCI-H526 CRL-5811, NCI-H209 HTB-172, NCI-H1105 CRL-5856, NCI-H187 CRL-5804, DMS79 CRL-2049, NCI-H146 HTB-173, NCI-H2171 CRL-5929, NCI-H1963 CRL-5982, NCI-H378 CRL-5808, Beas-2B CRL-3588; DSMZ: HCC33 487), SCLC-16HC and the NSCLC cell line (ATCC: NCI-H1944 CRL-5907) were cultivated in RPMI-1640 (Gibco).

Techniques: Expressing, Derivative Assay, Two Tailed Test, Western Blot

Journal: Nature Communications

Article Title: Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy

doi: 10.1038/s41467-026-71608-4

Figure Lengend Snippet: A The NRF2 protein level in total cell extracts was analyzed in SCLC and non-cancerous cell lines upon treatment with DMSO (control) or CDDO-Me by immunoblotting. NRF2 expression in DMSO-treated H82 cells was set to 1 for each experiment. Relative data represent mean ± SD of two independent experiments for H2171, H146, DMS79, H378, 16HC, H187, and HCC33, and at least three independent experiments for the other cell lines. Statistical significance was assessed using a two-tailed unpaired t -test. Exact p values are indicated in the figure when significant (<0.05). B The induction of NQO1 and AKR1C3 transcripts upon CDDO-Me treatment in different cell lines was determined by expression profiling ( n = 3, mean ± SD, two-tailed unpaired t- test). Exact p values are indicated in the figure when significant (<0.05). C The induction of NQO1 and AKR1C3 proteins upon CDDO-Me (50 nM) treatment was determined by immunoblotting (representative of three independent experiments). D The top 45 genes highly correlated with resistance to TXNRD1 inhibition were analyzed by expression profiling of two non-cancerous and two SCLC cell lines treated with CDDO-Me compared to a DMSO control ( n = 3). ACBs are labeled in blue. E The most upregulated pathways upon CDDO-Me treatment according to a pathway enrichment analysis based on mRNA expression profiling data using Ingenuity Pathway Analysis (IPA, QIAGEN Inc., Redwood City, CA, USA). Canonical pathway enrichment was assessed using right-tailed Fisher’s exact test, and p value were adjusted for multiple testing where applicable. F Oxidized and reduced levels of PRDX1 protein were analyzed by immunoblotting in cells treated first with CDDO-Me (50 nM) for 24 h and then with the indicated concentrations of DKFZ-682 for 3 h. Bar diagrams summarize the quantitative results from independent experiments ( n = 2 for H526, H82 and Beas-2B, n = 4 for HaCaT, mean ± SD). Statistical significance was assessed using a two-tailed unpaired t -test. Exact p values are indicated in the figure when significant (<0.05). G The cells were treated with CDDO-Me (50 nM) or DMSO (control). After 24 h, a concentration series of DKFZ-682 was added for another 24 h and the cell viability was measured by the CellTiter-Glo assay. The fold change of EC 50 for DKFZ-682 upon CDDO-Me compared to cells without CDDO-Me pretreatment was calculated. Source data are provided as a file.

Article Snippet: Human SCLC suspension cell lines (ATCC: NCI-H69 HTB-119, NCI-H82 HTB-175, NCI-H526 CRL-5811, NCI-H209 HTB-172, NCI-H1105 CRL-5856, NCI-H187 CRL-5804, DMS79 CRL-2049, NCI-H146 HTB-173, NCI-H2171 CRL-5929, NCI-H1963 CRL-5982, NCI-H378 CRL-5808, Beas-2B CRL-3588; DSMZ: HCC33 487), SCLC-16HC and the NSCLC cell line (ATCC: NCI-H1944 CRL-5907) were cultivated in RPMI-1640 (Gibco).

Techniques: Control, Western Blot, Expressing, Two Tailed Test, Inhibition, Labeling, Concentration Assay, Glo Assay

Journal: Nature Communications

Article Title: Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy

doi: 10.1038/s41467-026-71608-4

Figure Lengend Snippet: Human SCLC cell line H209 was transplanted subcutaneously into nude mice (for details see method section Animal experiments). Tumor-bearing mice were distributed into groups ( n = 10) and treated with vehicle (black), cisplatin/etoposide (gray, chemo, receiving 3 weekly cycles of cisplatin 3 mg/kg, interperitonally, i.p., on Monday and etoposide 7.5 mg/kg, i.p., on Wednesday and Friday) or daily injections of DKFZ-608 (green, starting with dose escalation of 5 - > 15 mg/kg in the first 5 days, continued with 15 mg/kg up to day 40). One group (blue) started on the chemo regimen for 3 weeks followed by DKFZ-608 for 40 days. The tumor size ( A ), survival ( B ) and body weight ( C ) were monitored during the course of the experiment. In ( A ), the mean values ± SD of the tumor size are shown and the group receiving DKFZ-608 mono-therapy (green) is presented as two separate lines in order to allow a better presentation of animals reaching full remission. The comparison of survival groups ( B ) was calculated with log-rank (Mantel-Cox) test. Tumor growth ( A ) and body weight ( C ), presented as mean ± SD, were analyzed using linear mixed-effects models with restricted maximum likelihood estimation (REML) via the lme4 package in R. The model included treatment (categorical), time (continuous; days), and their interaction as fixed effects, with random intercepts for individual animals to account for repeated measurements. Post-hoc pairwise comparisons between treatments were conducted using estimated marginal means in the emmeans package, with Tukey-adjusted p values. Source data are provided as a file.

Article Snippet: Human SCLC suspension cell lines (ATCC: NCI-H69 HTB-119, NCI-H82 HTB-175, NCI-H526 CRL-5811, NCI-H209 HTB-172, NCI-H1105 CRL-5856, NCI-H187 CRL-5804, DMS79 CRL-2049, NCI-H146 HTB-173, NCI-H2171 CRL-5929, NCI-H1963 CRL-5982, NCI-H378 CRL-5808, Beas-2B CRL-3588; DSMZ: HCC33 487), SCLC-16HC and the NSCLC cell line (ATCC: NCI-H1944 CRL-5907) were cultivated in RPMI-1640 (Gibco).

Techniques: Comparison

Journal: Nature Communications

Article Title: Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy

doi: 10.1038/s41467-026-71608-4

Figure Lengend Snippet: A As a tumor model, NSG mice were engrafted subcutaneously with the human SCLC cell line H526 (for details see “Method” section Animal experiments). After CDDO-Me pre-treatment, the NSG mice were daily injected intraperitoneally with DKFZ-682, gradually increasing the dose from 4 mg/kg to 10 mg/kg that was then maintained for up to 3 weeks. The tumor size was monitored daily for reaching the humane end-points. B Mice were randomly distributed into groups ( n = 10) that were daily injected with vehicle, CDDO-Me (3 mg/kg), a low dose of DKFZ-682 (dose escalation from 1 mg/kg to 4 mg/kg), CDDO-Me (3 mg/kg) and a low dose of DKFZ-682 (4 mg/kg), CDDO-Me (3 mg/kg) and a high dose of DKFZ-682 (dose escalation from 4 mg/kg to 10 mg/kg). The plot shows the survival of individual groups (compated by the log-rank (Mantel-Cox) test). C , D Impact of CDDO-Me and DKFZ-682 treatment on TXNRD1 activity and protein levels in tumor and liver tissue derived from treated mice (mean ± SD; n = 6 animals per group, measured in technical duplicates). The residual enzymatic activity of TXNRD1 in resected tumor and liver tissue was assessed by the activity probe TRFS-Green. Significance of differences was calculated with a two-tailed unpaired t -test. E The pathways upregulated by CDDO-Me were analyzed in mouse tissues and tumors, performing RNAseq. Samples from tumor-bearing mice (H526 tumors) that were injected with CDDO-Me (3 mg/kg) for 4 days were compared to vehicle ( n = 5). Pathway enrichment analysis was performed using Ingenuity Pathway Analysis (IPA, QIAGEN Inc., Redwood City, CA, USA). Canonical pathway enrichment was assessed using right-tailed Fisher’s exact test, and p values were adjusted for multiple testing where applicable. F The tumor size measured 12 days after the daily mouse treatment was started ( n = 10, one-way ANOVA p = 0.0025; pairwise differences compared by two-tailed unpaired t -test). G The sensitivity to DKFZ-682 was tested in explanted tumors after mouse treatment for the indicated time. Tumor cells were treated with a concentration series of DKFZ-682 for 24 h and cell viability was quantified using CellTiter-Glo. Each dot represents a tumor from one mouse measured in a triplicate. Source data are provided as a file.

Article Snippet: Human SCLC suspension cell lines (ATCC: NCI-H69 HTB-119, NCI-H82 HTB-175, NCI-H526 CRL-5811, NCI-H209 HTB-172, NCI-H1105 CRL-5856, NCI-H187 CRL-5804, DMS79 CRL-2049, NCI-H146 HTB-173, NCI-H2171 CRL-5929, NCI-H1963 CRL-5982, NCI-H378 CRL-5808, Beas-2B CRL-3588; DSMZ: HCC33 487), SCLC-16HC and the NSCLC cell line (ATCC: NCI-H1944 CRL-5907) were cultivated in RPMI-1640 (Gibco).

Techniques: Injection, Activity Assay, Derivative Assay, Two Tailed Test, RNA sequencing, Concentration Assay

Journal: Communications Biology

Article Title: PRC2 loss impairs small cell lung cancer tumorigenesis and enhances sensitivity to G9a/GLP inhibition

doi: 10.1038/s42003-026-09677-w

Figure Lengend Snippet: A Tumor incidence in control (Rb1 –/– ;Trp53 –/– ) mice and Eed knockout (Rb1 –/– ;Trp53 –/– ;Eed –/– ) mice. The number of mice per group and time point are mentioned in the table. B HE and Immunohistochemistry staining of lung sections 20 weeks post tumor initiation. Lungs are stained for NE marker (Synaptophysin), and PRC2 target (H3k27me3). All images have a scale bar of 50 μM. C Kaplan-Meier graph showing the percentage survival of control and Eed knockout mice ( n = 13) in days post tumor initiation. D Number of Eed +/– C584 cells ( n = 3) following 72 h treatment of control or CMV-Cre treatment. E Annexin V / PI staining of cells mentioned in ( D ). F Cell viability assay performed on mouse SCLC cell lines (RPKO1 and RPKO2) and mouse LUAD cell line KP141 treated with EED Protac degrader. G Cell viability assay performed on human SCLC cell lines (H69, H82, H187, DMS273, DMS114 and SW1271) and human LUAD cell lines (A549 and PC9) treated with EED Protac degrader. LUAD cell lines are shown in red. Neuroendocrine (NE) SCLC cells are shown in green. Non-NE SCLC cell lines are shown in blue. All data is shown as mean ± SD.

Article Snippet: Human SCLC cell lines (DMS114 and SW1271) and mesothelioma cell lines (H2731, H2810, and H2818) were obtained from ATCC and cultured in the same medium as above.

Techniques: Control, Knock-Out, Immunohistochemistry, Staining, Marker, Viability Assay