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Frontiers in Pharmacology logoLink to Frontiers in Pharmacology
. 2026 Feb 12;17:1788169. doi: 10.3389/fphar.2026.1788169

Correction: Network pharmacology, bioinformatics and in vitro/in vivo validation elucidate the anti-lung cancer activities and potential targets of Rhoifolin

Jing Qian 1,, Wei Cheng 2,, Shuangyan Li 3, Li Deng 4, Di Gao 5, Xue Zhang 1, Yunhui Zhang 1,*
PMCID: PMC12936559  PMID: 41769693

There was a mistake in Figures 2, 3, 6 as published. In Figures 2F,G, 3D, 6A,D, the compound name “Rhoifolin” was incorrectly spelled as “Phoifolin” in the bar graph for cell lines H358 and H1299. In Figure 2B, the legend label for the “48 h” time point was incorrectly written as “48 4”. In Figure 3D, the asterisks indicating statistical significance on the bar graph were omitted. The corrected Figures 2, 3, 6 appear below.

FIGURE 2.

Panel figure showing effects of Rhoifolin on H358 and H1299 cells. Panels A and C display scratch wound healing assays across increasing Rhoifolin concentrations and time points, with reduced closure at higher doses. Panels B and D present bar graphs quantifying reduced scratch closure rates for both cell lines. Panel E shows images of cell invasion assays, with fewer stained cells at higher Rhoifolin doses. Panels F and G quantify invasion by bar graphs, indicating decreased invasion with higher drug concentrations. Panels H and J show Western blots for E-cadherin and N-cadherin expression, with panels I and K presenting bar graphs of quantification in H358 and H1299 cells, respectively.

Effect of Rhoifolin on lung cancer cell migration and invasion. (A–D) Scratch assay showing the effect of Rhoifolin on the migration of H358 and H1299 cells. (E–G) Transwell invasion assays showing the effect of Rhoifolin on the invasion ability of H358 and H1299 cells. (H–K) Western blot analysis of EMT-related markers E-cadherin and N-cadherin in H358 and H1299 cells treated with Rhoifolin. Statistical significance was determined using p-values, with *p < 0.05, **p < 0.01, and ***p < 0.001 indicating significant differences between groups. “ns” denotes no statistical significance.

FIGURE 3.

Panel A shows flow cytometry histograms and bar charts demonstrating cell cycle distribution in H358 and H1299 cells treated with different concentrations of rhoifolin or DMSO; an increase in G2/M phase population is evident. Panels B and C display western blot bands and quantification for CDK1 and cyclin B1 protein expression, revealing decreased levels with increasing rhoifolin in H358 (panel B) and H1299 (panel C) cells. Panel D consists of dot plots and bar graphs showing apoptosis in H358 and H1299 cells, with apoptotic rate increasing in a dose-dependent manner upon rhoifolin treatment. Panels E and F present western blots and quantification for BCL2 and BAX proteins, indicating reduced BCL2 and elevated BAX in H358 (panel E) and H1299 (panel F) cells with higher rhoifolin concentration.

Effect of Rhoifolin on lung cancer cell cycle and apoptosis. (A) Flow cytometry analysis showing the effect of Rhoifolin on the cell cycle distribution of H358 and H1299 cells. (B,C) Western blot analysis of cell cycle proteins (CDK1,Cyclin B1) in the Rhoifolin-treated H358 and H1299 cells. (D) Flow cytometry analysis of apoptosis in H358 and H1299 cells treated with Rhoifolin. (E,F) Western blot analysis of apoptotic regulatory proteins (Bax and Bcl-2) in Rhoifolin-treated H358 and H1299 cells. Statistical significance was determined using p-values, with *p < 0.05, **p < 0.01, and ***p < 0.001 indicating significant differences between groups. “ns” denotes no statistical significance.

FIGURE 6.

Panel A shows a bar graph of EPHB2 mRNA expression levels in H358 cells treated with DMSO or increasing concentrations of rhoifolin, with expression decreasing as concentration increases. Panel B presents immunofluorescence images with DAPI and EPHB2 staining in H358 cells, showing reduced EPHB2 signal with higher rhoifolin doses. Panel C shows a western blot for EPHB2 and GAPDH with decreasing EPHB2 protein at higher rhoifolin concentrations. Panel D shows a bar graph quantifying EPHB2 protein levels, confirming the reduction. Panel E displays a molecular surface representation of EPHB2 bound to rhoifolin, including a zoomed molecular interaction view. Panels F to N include line graphs, bar charts, and a 3D energy surface plot depicting molecular dynamics parameters, RMSD, binding free energy changes, and residue contributions for EPHB2-rhoifolin interaction.

Verification of Rhoifolin potential targeting EPHB2. (A) qRT-PCR analysis of EPHB2 mRNA expression in H358 cells treated with Rhoifolin. (B) Immunofluorescence observation of EPHB2 protein localization and expression. (C,D) Western blot analysis of EPHB2 protein expression in H358 cells treated with Rhoifolin. (E) Molecular docking simulation of Rhoifolin binding to EPHB2. (F) RMSD analysis of the protein-ligand complex during the simulation. (G) RMSF analysis of the protein-ligand complex during the simulation. (H) Radius of gyration (Rg) analysis of the protein-ligand complex. (I) SASA analysis of the protein-ligand complex. (J) Hydrogen bond analysis of the protein-ligand complex during the simulation. (K) Free energy landscape of the protein-ligand complex during the simulation. (L) Dynamic change in binding free energy of the Rhoifolin-EPHB2 complex during 100 ns simulation. (M) Total binding free energy of the Rhoifolin-EPHB2 complex. (N) Free energy decomposition analysis of key residues in the Rhoifolin-EPHB2 complex.

The original article has been updated.

Footnotes

Edited and reviewed by: Vanessa Souza-Mello, Rio de Janeiro State University, Brazil

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