Journal: Research

Article Title: Natural Flavonoids Genistein and Baicalein as Well-Tolerated Radiosensitizers to Enhance the Efficacy of 177 Lu-PSMA617 in Prostate Cancer: In Vitro and In Vivo Studies

doi: 10.34133/research.1314

Figure Lengend Snippet: Transcriptomic profiling reveals differential responses to flavonoids in LNCaP cells. (A) Volcano plots of DEGs after genistein (left) or baicalein (right) treatment (20 μM, 24 h). Baicalein elicited stronger fold changes; genistein’s effects were broader but milder. (B) Heatmap of key genes across 4 functional modules. Baicalein induced coherent pro-apoptotic/anti-repair reprogramming; genistein’s changes were more subtle. (C) KEGG pathway enrichment for baicalein (top 8 significant terms). (D) Pathway-interaction networks modulated by genistein (left) and baicalein (right). Node color indicates regulation direction/magnitude; edge thickness represents modulation strength. Values denote average fold change per pathway.

Article Snippet: For monotherapy studies, genistein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. G810424), baicalein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. B802462), and 177 Lu-PSMA617 (0.37, 1.85, 3.7, 9.25, and 18.5 kBq per well) were dissolved in dimethyl sulfoxide (DMSO; Macklin, Shanghai, China; catalog no. D8418) to treat cells, with a final concentration of <0.1%.

Techniques: Functional Assay

Journal: Research

Article Title: Natural Flavonoids Genistein and Baicalein as Well-Tolerated Radiosensitizers to Enhance the Efficacy of 177 Lu-PSMA617 in Prostate Cancer: In Vitro and In Vivo Studies

doi: 10.34133/research.1314

Figure Lengend Snippet: Enhanced radiosensitization and mechanistic insights of genistein and baicalein combined with 177 Lu-PSMA617 in LNCaP cells. (A) Dose–response curve and IC 50 value for genistein monotherapy. (B) Dose–response curve and IC 50 value for baicalein monotherapy. (C) Dose–response curves of 177 Lu-PSMA617 combined with increasing concentrations of genistein. Cotreatment reduced the IC 50 of 177 Lu-PSMA617 in a dose-dependent manner. (D) Dose–response curves of 177 Lu-PSMA617 combined with increasing concentrations of baicalein. Cotreatment reduced the IC 50 of 177 Lu-PSMA617 in a dose-dependent manner. (E) Heatmap depicting combination index (CI) values derived using the Chou–Talalay method: CI < 0.8 indicates synergy. (F) Levels of ROS (left), γ-H2AX (middle), and cleaved caspase-3 (right). Combination treatments significantly elevated all markers versus corresponding monotherapies ( P < 0.05). (G) Western blot analysis demonstrating that combination treatments significantly reduced the p-AKT/t-AKT ratio compared with control ( P < 0.01). (H) Schematic model depicting the proposed multi-targeted synergistic mechanism of genistein and baicalein in enhancing 177 Lu-PSMA617-induced cytotoxicity in LNCaP cells. (I) Membrane binding kinetics, which showed no significant effects or their interaction ( P > 0.05). Data are presented as mean ± SD ( n = 3 to 5 per group). *** P < 0.05, ** P < 0.01, * P < 0.001 versus the indicated control or between groups as shown.

Article Snippet: For monotherapy studies, genistein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. G810424), baicalein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. B802462), and 177 Lu-PSMA617 (0.37, 1.85, 3.7, 9.25, and 18.5 kBq per well) were dissolved in dimethyl sulfoxide (DMSO; Macklin, Shanghai, China; catalog no. D8418) to treat cells, with a final concentration of <0.1%.

Techniques: Derivative Assay, Western Blot, Control, Membrane, Binding Assay

Journal: Research

Article Title: Natural Flavonoids Genistein and Baicalein as Well-Tolerated Radiosensitizers to Enhance the Efficacy of 177 Lu-PSMA617 in Prostate Cancer: In Vitro and In Vivo Studies

doi: 10.34133/research.1314

Figure Lengend Snippet: Assessment of treatment-related toxicity in liver and kidney tissues. (A to L) Representative H&E-stained sections of liver (A to F) and kidney (G to L) from treated mice. Liver sections (A to F): (A) Control group, showing normal hepatic architecture. (B) 177 Lu-PSMA617 monotherapy group, with minimal changes (mild central venous congestion and scattered inflammation). (C) 177 Lu-PSMA617 + genistein combination group. (D) 177 Lu-PSMA617 + baicalein combination group. (E) Genistein monotherapy group. (F) Baicalein monotherapy group. Livers from combination and flavonoid-alone groups (C) to (F) remained largely intact, with occasional mild hepatocyte swelling noted in (C). Kidney sections (G to L): (G) Control group. (H) 177 Lu-PSMA617 monotherapy group, showing mild nephrotoxicity (vacuolation and swelling of proximal tubular epithelial cells). (I) 177 Lu-PSMA617 + genistein combination group. (J) 177 Lu-PSMA617 + baicalein combination group. (K) Genistein monotherapy group. (L) Baicalein monotherapy group. Combination therapies (I and J) did not exacerbate renal damage compared to monotherapy (H). For each organ, images are presented at 3 magnifications: (a) low (20×), (b) medium (40×), and (c) high (60×). Scale bars, 100 μm (20×), 50 μm (40×), and 20 μm (60×).

Article Snippet: For monotherapy studies, genistein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. G810424), baicalein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. B802462), and 177 Lu-PSMA617 (0.37, 1.85, 3.7, 9.25, and 18.5 kBq per well) were dissolved in dimethyl sulfoxide (DMSO; Macklin, Shanghai, China; catalog no. D8418) to treat cells, with a final concentration of <0.1%.

Techniques: Staining, Control

Journal: Research

Article Title: Natural Flavonoids Genistein and Baicalein as Well-Tolerated Radiosensitizers to Enhance the Efficacy of 177 Lu-PSMA617 in Prostate Cancer: In Vitro and In Vivo Studies

doi: 10.34133/research.1314

Figure Lengend Snippet: Histopathological analysis of tumor tissues following combination therapy. (A to F) Representative H&E-stained sections of LNCaP xenograft tumors. (A) Control (saline). (B) Genistein alone. (C) Baicalein alone. (D) 177 Lu-PSMA617 alone, showing focal damage. (E) 177 Lu-PSMA617 + genistein, showing extensive necrosis, fibrosis, and inflammation. (F) 177 Lu-PSMA617 + baicalein, showing enhanced damage. (D to F) Left panel: overview (scale bar, 200 μm; 10× magnification); middle panel: intermediate-magnification view (scale bar, 100 μm; 20× magnification); right panels (top to bottom): high-magnification views of necrosis, fibrosis, and inflammation (scale bar, 50 μm; 40× magnification). (A to C) Single overview image is shown (scale bar, 200 μm). (G and H) Quantitative analysis of necrosis, fibrosis, inflammation, and apoptosis. Data are mean ± SD ( n = 3). * P < 0.05, **** P < 0.0001.

Article Snippet: For monotherapy studies, genistein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. G810424), baicalein (1, 10, 20, 30, 50, 100, and 200 μM; Macklin Inc., Shanghai, China; catalog no. B802462), and 177 Lu-PSMA617 (0.37, 1.85, 3.7, 9.25, and 18.5 kBq per well) were dissolved in dimethyl sulfoxide (DMSO; Macklin, Shanghai, China; catalog no. D8418) to treat cells, with a final concentration of <0.1%.

Techniques: Staining, Control, Saline