Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 inhibits the proliferation, colony formation, and stemness of NSCLC cells. A Chemical structure of LB42708. B IC 50 values for LB42708 and tipifarnib in NCI-H1915 cells. C NCI-H1915 cells were treated with various concentrations of LB42708 for the indicated durations, and cell proliferation was assessed using the CCK-8 assay ( n = 6). D IC 50 values for LB42708 and tipifarnib in A549 cells. E Cell proliferation of A549 cells treated with varying concentrations of LB42708 for the indicated times was measured using the CCK-8 assay ( n = 6). F-I IC 50 values for LB42708 in NCI-H1299 ( F ), NCI-H520 ( G ), PC9 ( H ) and HPAEpiC ( I ) cells. J and K Effect of LB42708 on colony formation in A549 ( J ) and NCI-H1915 ( K ) cells. Cells were treated with the indicated concentrations of LB42708 and incubated for 2 weeks. Colonies were fixed, stained, and quantified using ImageJ ( n = 3). L and M EdU incorporation assays were applied to examine the EdU positive A549 ( L ) and NCI-H1915 ( M ) cells after treatment with LB42708 for 48 h ( n = 3). Scale bar = 100 μm. N Representative images of tumorsphere formation assays for A549 and NCI-H1915 cells treated with indicated concentrations of LB42708. Scale bar = 100 μm. O and P Quantification of tumorsphere number ( O ) and diameter ( P ) for A549 and NCI-H1915 cells ( n = 3). Data are shown as the mean ± SD. Significance was determined by one-way ANOVA with Dunnett’s test (* P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 vs. control)

Article Snippet: The cell lines NCI-H1915 and NCI-H1299 were purchased from the American Type Culture Collection (ATCC).

Techniques: CCK-8 Assay, Incubation, Staining, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 inhibits the migration, invasion, and adhesion of A549 and NCI-H1915 cells. A and B Wound healing assay of A549 ( A ) and NCI-H1915 ( B ) cells treated with various concentrations of LB42708. Representative images were captured at 0, 24, 48, or 72 h post-scratch. C and D Quantification of wound closure for A549 ( C ) and NCI-H1915 ( D ) cells is shown ( n = 3). E-J The effects of LB42708 on the migration and invasion of A549 ( E–G ) and NCI-H1915 ( H–J ) cells were evaluated using a Transwell assay without (migration; upper panels of E and H) or with Matrigel coating (invasion; lower panels of E and H). Scale bar = 100 μm. Quantification of migrated cell numbers and relative invasive areas is shown for A549 ( F and G ) and NCI-H1915 ( I and J ) cells ( n = 3). K and L The effect of LB42708 on the adhesion ability of A549 ( K ) and NCI-H1915 ( L ) cells was assessed using a cell adhesion assay ( n = 5). Data are shown as the mean ± SD. Significance was determined by one-way ANOVA with Dunnett’s test (* P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 vs. control, ns, not significant.)

Article Snippet: The cell lines NCI-H1915 and NCI-H1299 were purchased from the American Type Culture Collection (ATCC).

Techniques: Migration, Wound Healing Assay, Transwell Assay, Cell Adhesion Assay, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 induces FTase α-subunit degradation via caspase-3 and RAS via the proteasome. A and B A549 ( A ) and NCI-H1915 ( B ) cells were treated with the indicated concentrations of LB42708 or 20 µM etoposide for 48 h, and FTase α-subunit levels were subsequently assessed by western blotting. C and D A549 ( C ) and NCI-H1915 ( D ) cells were pretreated with the pan-caspase inhibitor Z-DEVD-FMK (10 µM, 2 h) prior to LB42708 (20 µM, 48 h) exposure. FTase α-subunit and cleaved caspase-3 levels were determined by western blotting. E and F NSCLC cells were treated with various concentrations of LB42708 for 48 h. KRAS and pan-RAS levels in A549 cells ( E ) and HRAS and pan-RAS levels in NCI-H1915 cells ( F ) were analyzed by western blotting. G and H A549 ( G ) and NCI-H1915 ( H ) cells were pretreated with the proteasome inhibitor bortezomib (40 nM, 2 h), followed by treatment with 20 µM LB42708 for 48 h. KRAS levels in A549 cells and HRAS levels in NCI-H1915 cells were assessed by western blotting. I and J A549 ( I ) and NCI-H1915 ( J ) cells were pretreated with the HECT E3 ubiquitin ligase inhibitor heclin (5 µM, 2 h), followed by treatment with LB42708 (20 µM) for 48 h. KRAS and pan-RAS levels in A549 cells, and HRAS and pan-RAS levels in NCI-H1915 cells were analyzed by western blotting. All experiments were performed at least three times independently. α-Actinin or GAPDH was used as a loading control. Data are presented as mean ± SD, and statistical significance was evaluated using one-way ANOVA followed by Dunnett’s test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns, not significant

Article Snippet: The cell lines NCI-H1915 and NCI-H1299 were purchased from the American Type Culture Collection (ATCC).

Techniques: Western Blot, Ubiquitin Proteomics, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: Synergistic anti-tumor effect of LB42708 combined with AKT inhibitor AZD5363 on RAS-mutant NSCLC cells. A and B A549 ( A ) and NCI-H1915 ( B ) were treated with increasing concentrations of LB42708 or 20 µM tipifarnib for 48 h, followed by western blot analysis of the expression and phosphorylation levels of the indicated proteins. C and F Fa-Dose plots showing the growth-inhibitory effects of LB42708 or AZD5363 on A549 ( C ) and NCI-H1915 ( F ) cells. D and G Fa-Dose plots illustrating the synergistic effects of LB42708 combined with AZD5363 on A549 ( D ) and NCI-H1915 ( G ) cell growth. E and H Fa-CI plot indicating synergism between LB42708 and AZD5363 in inhibiting the proliferation of A549 ( E ) and NCI-H1915 ( H ) cells. I and J A549 ( I ) and NCI-H1915 ( J ) cells were treated with 5 or 10 µM LB42708, AZD5363, or their combination for 48 h. The expression and phosphorylation levels of the indicated proteins were analyzed by western blotting. All experiments were independently repeated a minimum of three times. Quantitative data are presented as mean ± SD. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s test. Significance levels were defined as * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 compared with the control group; ns indicates no statistically significant difference

Article Snippet: The cell lines NCI-H1915 and NCI-H1299 were purchased from the American Type Culture Collection (ATCC).

Techniques: Mutagenesis, Western Blot, Expressing, Phospho-proteomics, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 and AZD5363 combination induces cell arrest at the G2/M or G1phase, and induces apoptosis. A and B Cell cycle distribution was determined by flow cytometry in A549 ( A ) and NCI-H1915 ( B ) cells following treatment with DMSO (control), 5 µM LB42708, 5 µM AZD5363, or their combination for 24 h. Results from three independent experiments were averaged, and the proportions of cells in each phase were plotted to illustrate cell cycle arrest. C and D Flow cytometry was used to assess apoptosis by detecting Annexin V-FITC and propidium iodide (PI) staining after 60 h of drug treatment (10 µM LB42708, 10 µM AZD5363, or their combination). The combined percentages of early and late apoptotic cells were calculated for each treatment group based on the average of three independent experiments and are presented as total apoptotic cell percentages. C A549 cells; D NCI-H1915 cells. E and F A549 ( E ) and NCI-H1915 ( F ) cells were treated with DMSO (control), 10 µM LB42708, 10 µM AZD5363, or their combination for 48 h. The levels of cleaved caspase-3 and caspase-7 were examined by western blotting. Quantitative results represent the average of three independent experiments and are expressed as mean ± SD. Statistical significance was evaluated using one-way ANOVA with Dunnett’s test. Differences versus the control group were considered significant at * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001; ns denotes no significant difference

Article Snippet: The cell lines NCI-H1915 and NCI-H1299 were purchased from the American Type Culture Collection (ATCC).

Techniques: Flow Cytometry, Control, Staining, Western Blot

Journal: Cell Communication and Signaling : CCS

Article Title: Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation

doi: 10.1186/s12964-026-02798-z

Figure Lengend Snippet: LB42708 inhibits the in vivo growth of RAS-mutant NSCLC tumors. A Schemes for the in vivo experimental procedures to evaluate anticancer activities of LB42708 and AZD5363. To evaluate the enhanced antitumor effect of combined treatment, NCI-H1915 tumor-bearing BALB/c nude mice (injected subcutaneously with 5 × 10⁶ cells per mouse) were administered vehicle, LB42708 (25 mg/kg), AZD5363 (25 mg/kg), or a combination of both via intraperitoneal injection for 15 consecutive days. B Xenograft tumors from each group were collected on day 20 ( n = 6 per group). C Tumor volumes were recorded throughout the study and expressed as mean ± SD ( n = 6 per group). D Final tumor weights were quantified and shown as mean ± SD in a histogram ( n = 6 per group). E Body weights of mice in each group were monitored and plotted over time. F Representative images of endpoint tumor tissues showing: H&E staining for histological features, Ki-67 immunohistochemistry for cell proliferation, and TUNEL staining for apoptosis. Scale bar = 100 μm. G and H Statistics data represent mean ± SD ( n = 6) of Ki67 ( G ) and TUNEL ( H ) for each group. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s test. Comparisons to the control group were marked as * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns indicates no significant difference. I and J A model illustrating the synergistic anti-tumor mechanisms of LB42708 and the AKT inhibitor AZD5363 in RAS-mutant NSCLC ( I ), and the mechanism by which LB42708 enhances the sensitivity of PC9GR cells to gefitinib ( J )

Article Snippet: The cell lines NCI-H1915 and NCI-H1299 were purchased from the American Type Culture Collection (ATCC).

Techniques: In Vivo, Mutagenesis, Injection, Staining, Immunohistochemistry, TUNEL Assay, Control

Journal: Cell reports

Article Title: TGF-β1-mediated intercellular signaling fuels cooperative cellular invasion

doi: 10.1016/j.celrep.2025.115315

Figure Lengend Snippet:

Article Snippet: H1915 , ATCC , Cat#CRL-5904; RRID: CVCL_1505.

Techniques: Recombinant, Reverse Transcription, Bicinchoninic Acid Protein Assay, Staining, RNA Sequencing