Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (5): 1106-1116.DOI: 10.19852/j.cnki.jtcm.2026.05.005
• Original Articles • Previous Articles Next Articles
Xuefu Zhuyu capsule (血府逐瘀胶囊) modulates angiogenesis in association with the Jagged1/Notch pathway in lung cancer and chemotherapy contexts
WANG Yizheng1,2, ZHANG Jiayu1,2, LI Yuxia1,2, FU Juanli1,2, PING Chunjia1,2, LI Yuxuan1,2, WANG He1,2, GAO Dong1,2, LIN Fan1,2(
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- 1
College of Integrative Medicine ,Fujian University of Traditional Chinese Medicine, Fuzhou Fujian 350122, China
2Academy of Integrative Medicine ,Fujian University of Traditional Chinese Medicine Fuzhou 350122, China
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Received:2025-08-12Accepted:2025-12-23Online:2026-10-15Published:2026-10-09 -
Contact:LIN Fan, College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. 2009037@fjtcm.edu.cn,Telephone: +86-591-22861151 -
About author:WANG Yizheng and ZHANG Jiayu are co-first authors and contributed equally to this work
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Supported by:National Natural Science Foundation of China: Mechanism of Xuefu Zhuyu Decoction Regulating Vascular Growth of Lung Cancer with Qi Stagnation and Blood Stasis through Delta-like Protein 4/Notch Signaling Pathway(82204969);Role and Mechanism of Krüppel-like Factor 2 Signaling in Promoting Angiogenesis by Xuefu Zhuyu Decoction under Fluid Shear Stress(82074191);Study on the Mechanism of Krüppel-like Factor 4/5 as a Molecular Switch in the Angiogenesis Signaling Network of Xuefuzhuyu Decoction(82304954);Natural Science Foundation of Fujian Province: the Role of Fructose-2, 6-bisphosphatase 3-Mediated Glycolysis in the Overall Regulation of Angiogenesis by Xuefu Zhuyu Decoction(2024J01748)
Cite this article
WANG Yizheng, ZHANG Jiayu, LI Yuxia, FU Juanli, PING Chunjia, LI Yuxuan, WANG He, GAO Dong, LIN Fan. Xuefu Zhuyu capsule (血府逐瘀胶囊) modulates angiogenesis in association with the Jagged1/Notch pathway in lung cancer and chemotherapy contexts[J]. Journal of Traditional Chinese Medicine, 2026, 46(5): 1106-1116.
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Figure 1 XFZYC combined with DDP inhibits angiogenesis of Lewis lung cancer xenografts A: laser speckle contrast imaging of tumor blood flow, red indicates blood flow signals; B: microvessel density was assessed by CD34 immunohistochemical staining in tumor tissues (× 400). Red arrows indicate microvessel locations. Scale bar, 50 μm; C: histogram of quantified blood perfusion values; D: graphical representation of tumor microvascular density measurements; A1, B1: Model group; A2, B2: DDP group; A3, B3: XFZYC group; A4, B4: XFZYC + DDP group. LLC tumor-bearing mice with successful tumor engraftment were randomly assigned into four groups. Model group: received normal saline by gavage twice daily; XFZYC group: administered XFZYC by gavage at a dose of 0.36 g/kg (converted from the adult human equivalent dose based on body surface area) twice daily. DDP group: received intraperitoneal injection of DDP at 2 mg/kg once every two days. XFZYC + DDP group: received both XFZYC by gavage at the same dose as the XFZYC group (twice daily) and intraperitoneal injection of DDP at 2 mg/kg once every two days. All treatments were continued for two consecutive weeks. XFZYC: Xuefu Zhuyu capsule; DDP: cisplatin; LLC: Lewis lung carcinoma. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 5 in A and n = 10 in B). aP < 0.01, bP < 0.05 vs Model group; cP < 0.05 vs DDP group.
Figure 1 XFZYC combined with DDP inhibits angiogenesis of Lewis lung cancer xenografts A: laser speckle contrast imaging of tumor blood flow, red indicates blood flow signals; B: microvessel density was assessed by CD34 immunohistochemical staining in tumor tissues (× 400). Red arrows indicate microvessel locations. Scale bar, 50 μm; C: histogram of quantified blood perfusion values; D: graphical representation of tumor microvascular density measurements; A1, B1: Model group; A2, B2: DDP group; A3, B3: XFZYC group; A4, B4: XFZYC + DDP group. LLC tumor-bearing mice with successful tumor engraftment were randomly assigned into four groups. Model group: received normal saline by gavage twice daily; XFZYC group: administered XFZYC by gavage at a dose of 0.36 g/kg (converted from the adult human equivalent dose based on body surface area) twice daily. DDP group: received intraperitoneal injection of DDP at 2 mg/kg once every two days. XFZYC + DDP group: received both XFZYC by gavage at the same dose as the XFZYC group (twice daily) and intraperitoneal injection of DDP at 2 mg/kg once every two days. All treatments were continued for two consecutive weeks. XFZYC: Xuefu Zhuyu capsule; DDP: cisplatin; LLC: Lewis lung carcinoma. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 5 in A and n = 10 in B). aP < 0.01, bP < 0.05 vs Model group; cP < 0.05 vs DDP group.
Figure 2 Effect of XFZYC combined with DDP on the expression of Notch signaling pathway and angiogenesis-related proteins in tumor tissues A: representative Western blot bands; B: relative protein expression of Jagged1; C: relative protein expression of Dll4; D: relative protein expression of Notch1 (NICD); E: relative protein expression of Hey1; F: relative protein expression of VEGFA; G: relative protein expression of VEGFR2. LLC tumor-bearing mice with successful tumor engraftment were randomly assigned into four groups. Model group: received normal saline by gavage twice daily; XFZYC group: administered XFZYC by gavage at a dose of 0.36 g/kg (converted from the adult human equivalent dose based on body surface area) twice daily. DDP group: received intraperitoneal injection of DDP at 2 mg/kg once every two days. XFZYC + DDP group: received both XFZYC by gavage at the same dose as the XFZYC group (twice daily) and intraperitoneal injection of DDP at 2 mg/kg once every two days. All treatments were continued for two consecutive weeks. XFZYC: Xuefu Zhuyu capsule; DDP: cisplatin; LLC: Lewis lung carcinoma; Dll4: delta-like protein 4; NICD: Notch 1 intracellular cytoplasmic domain; VEGFA: vascular endothelial growth factor A; VEGFR2: Vascular endothelial growth factor receptor 2. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 3). aP < 0.01, dP < 0.05 vs Model group; bP < 0.05, cP < 0.05 vs DDP group.
Figure 2 Effect of XFZYC combined with DDP on the expression of Notch signaling pathway and angiogenesis-related proteins in tumor tissues A: representative Western blot bands; B: relative protein expression of Jagged1; C: relative protein expression of Dll4; D: relative protein expression of Notch1 (NICD); E: relative protein expression of Hey1; F: relative protein expression of VEGFA; G: relative protein expression of VEGFR2. LLC tumor-bearing mice with successful tumor engraftment were randomly assigned into four groups. Model group: received normal saline by gavage twice daily; XFZYC group: administered XFZYC by gavage at a dose of 0.36 g/kg (converted from the adult human equivalent dose based on body surface area) twice daily. DDP group: received intraperitoneal injection of DDP at 2 mg/kg once every two days. XFZYC + DDP group: received both XFZYC by gavage at the same dose as the XFZYC group (twice daily) and intraperitoneal injection of DDP at 2 mg/kg once every two days. All treatments were continued for two consecutive weeks. XFZYC: Xuefu Zhuyu capsule; DDP: cisplatin; LLC: Lewis lung carcinoma; Dll4: delta-like protein 4; NICD: Notch 1 intracellular cytoplasmic domain; VEGFA: vascular endothelial growth factor A; VEGFR2: Vascular endothelial growth factor receptor 2. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 3). aP < 0.01, dP < 0.05 vs Model group; bP < 0.05, cP < 0.05 vs DDP group.
Figure 3 XFZY-CS inhibits angiogenesis of C166 cells in a tumor chemotherapy environment A: representative images of in vitro Matrigel tube formation assay (× 200). Scale bar, 200μm; B: quantification of junctions; C: quantification of tubular length; D: VEGFA concentration in cell culture supernatant; E: bFGF concentration in cell culture supernatant; F: EGF concentration in cell culture supernatant; G: TGF-β concentration in cell culture supernatant. A1, A5: Control group; A2, A6: DDP group; A3, A7: Coculture group; A4, A8: Coculture + DDP group. Control group: C166 cells cultured alone without DDP treatment.; DDP group: C166 cells cultured alone and treated with DDP for 24 h; Coculture group: C166 cells cocultured with LLC cells without DDP treatment; Coculture + DDP group: C166 cells cocultured with LLC cells and treated with DDP for 24 h. Control-S: Control serum-treated C166 cell group; XFZY-CS: XFZYC-containing serum-treated C166 cell group. LLC: Lewis lung cancer cells; DDP: cisplatin; VEGFA: vascular endothelial growth factor A; bFGF: basic fibroblast growth factor; EGF: epidermal growth factor; TGF-β: transforming growth factor-beta. Comparisons between two groups were conducted using Student's t-test. Data are presented as mean ± standard deviation (n = 5 for B and C; n = 6 for D, E, F and G). Compare with the model group, aP < 0.01, bP < 0.05 vs Control-S.
Figure 3 XFZY-CS inhibits angiogenesis of C166 cells in a tumor chemotherapy environment A: representative images of in vitro Matrigel tube formation assay (× 200). Scale bar, 200μm; B: quantification of junctions; C: quantification of tubular length; D: VEGFA concentration in cell culture supernatant; E: bFGF concentration in cell culture supernatant; F: EGF concentration in cell culture supernatant; G: TGF-β concentration in cell culture supernatant. A1, A5: Control group; A2, A6: DDP group; A3, A7: Coculture group; A4, A8: Coculture + DDP group. Control group: C166 cells cultured alone without DDP treatment.; DDP group: C166 cells cultured alone and treated with DDP for 24 h; Coculture group: C166 cells cocultured with LLC cells without DDP treatment; Coculture + DDP group: C166 cells cocultured with LLC cells and treated with DDP for 24 h. Control-S: Control serum-treated C166 cell group; XFZY-CS: XFZYC-containing serum-treated C166 cell group. LLC: Lewis lung cancer cells; DDP: cisplatin; VEGFA: vascular endothelial growth factor A; bFGF: basic fibroblast growth factor; EGF: epidermal growth factor; TGF-β: transforming growth factor-beta. Comparisons between two groups were conducted using Student's t-test. Data are presented as mean ± standard deviation (n = 5 for B and C; n = 6 for D, E, F and G). Compare with the model group, aP < 0.01, bP < 0.05 vs Control-S.
Figure 4 XFZYC suppresses angiogenesis by inhibiting Jagged1 in the lung cancer chemotherapy microenvironment A: representative western blot bands showing Jagged1 protein expression in C166 cells treated with different drugs; B: relative expression levels of Jagged1 in C166 cells among various treatment groups; C: representative western blot bands of Jagged1 protein expression in Jagged1-overexpressing C166 cells; D: relative expression levels of Jagged1 in Jagged1-overexpressing C166 cells; E: tube formation capacity of C166 cells transfected with Jagged1-overexpressing vector (× 200); F: quantification of junction numbers in Jagged1-overexpressing C166 cells; G: quantification of total tube length in Jagged1-overexpressing C166 cells; H: effect of XFZY-CS on tube formation ability of Jagged1-overexpressing C166 cells in the tumor chemotherapy microenvironment (× 200); I: quantification of junction numbers in Jagged1-overexpressing C166 cells treated with XFZY-CS in a chemotherapeutic environment; J: quantification of total tube length in Jagged1-overexpressing C166 cells treated with XFZY-CS in a chemotherapeutic environment; E1: Control; E2: NC; E3: OE-Jagged1; H1, H5: negative control C166 cells cocultured with LLC cells without DDP treatment; H2, H6: negative control C166 cells cocultured with LLC cells and treated with DDP for 24 h; H3, H7: Jagged1-overexpressing C166 cells cocultured with LLC cells without DDP treatment; H4, H8: Jagged1-overexpressing C166 cells cocultured with LLC cells and treated with DDP for 24 h. Control-S: Control serum-treated C166 cell group; XFZY-CS: XFZYC-containing serum-treated C166 cell group. LLC: Lewis lung cancer cells; DDP: cisplatin; Control: non-lentivirus-transfected C166 cells; NC: negative control lentivirus-transfected C166 cells; OE-Jagged1: Jagged1-overexpressing C166 cells. Scale bar, 200 μm. Comparisons between two groups were conducted using Student's t-test (in B, I, and J), while one-way analysis of variance was employed for multiple group comparisons (in D, F, and G). Data are presented as mean ± standard deviation (n = 3 for B and D; n = 5 for F, G, I, and J). aP < 0.05, eP < 0.01 vs Control-S; bP < 0.01 vs control group; cP < 0.01, dP < 0.05 vs NC group.
Figure 4 XFZYC suppresses angiogenesis by inhibiting Jagged1 in the lung cancer chemotherapy microenvironment A: representative western blot bands showing Jagged1 protein expression in C166 cells treated with different drugs; B: relative expression levels of Jagged1 in C166 cells among various treatment groups; C: representative western blot bands of Jagged1 protein expression in Jagged1-overexpressing C166 cells; D: relative expression levels of Jagged1 in Jagged1-overexpressing C166 cells; E: tube formation capacity of C166 cells transfected with Jagged1-overexpressing vector (× 200); F: quantification of junction numbers in Jagged1-overexpressing C166 cells; G: quantification of total tube length in Jagged1-overexpressing C166 cells; H: effect of XFZY-CS on tube formation ability of Jagged1-overexpressing C166 cells in the tumor chemotherapy microenvironment (× 200); I: quantification of junction numbers in Jagged1-overexpressing C166 cells treated with XFZY-CS in a chemotherapeutic environment; J: quantification of total tube length in Jagged1-overexpressing C166 cells treated with XFZY-CS in a chemotherapeutic environment; E1: Control; E2: NC; E3: OE-Jagged1; H1, H5: negative control C166 cells cocultured with LLC cells without DDP treatment; H2, H6: negative control C166 cells cocultured with LLC cells and treated with DDP for 24 h; H3, H7: Jagged1-overexpressing C166 cells cocultured with LLC cells without DDP treatment; H4, H8: Jagged1-overexpressing C166 cells cocultured with LLC cells and treated with DDP for 24 h. Control-S: Control serum-treated C166 cell group; XFZY-CS: XFZYC-containing serum-treated C166 cell group. LLC: Lewis lung cancer cells; DDP: cisplatin; Control: non-lentivirus-transfected C166 cells; NC: negative control lentivirus-transfected C166 cells; OE-Jagged1: Jagged1-overexpressing C166 cells. Scale bar, 200 μm. Comparisons between two groups were conducted using Student's t-test (in B, I, and J), while one-way analysis of variance was employed for multiple group comparisons (in D, F, and G). Data are presented as mean ± standard deviation (n = 3 for B and D; n = 5 for F, G, I, and J). aP < 0.05, eP < 0.01 vs Control-S; bP < 0.01 vs control group; cP < 0.01, dP < 0.05 vs NC group.
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