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Liposomal curcumin inhibits hypoxia-induced angiogenesis after transcatheter arterial embolization in VX2 rabbit liver tumors.

Dai F, Zhang X, Shen W, Chen J, Liu L, Gao G - Onco Targets Ther (2015)

Bottom Line: The levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P<0.05).There was a slight decrease in tumor size in the liposomal curcumin TAE-treated group at third-day time points compared to the TAE-treated group; the difference was not statistically significant (P>0.05).A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).

View Article: PubMed Central - PubMed

Affiliation: The First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China ; Department of Interventional Radiology, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, People's Republic of China.

ABSTRACT

Purpose: The purpose of the study is to investigate the inhibition of hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors by liposomal curcumin.

Materials and methods: A total of 54 VX2 rabbits were divided into three groups, and each group had three subgroups according to the sacrifice time. The animals in the control group (n=18) underwent sham embolization. Transcatheter arterial embolization (TAE)-treated group (n=18) animals underwent embolization with lipiodol (0.1 mL/kg body weight) and 90-180 µm polyvinyl alcohol (PVA) particles. Liposomal curcumin TAE-treated group (n=18) animals underwent embolization with liposomal curcumin (20 mg/kg body weight) mixed with lipiodol (0.1 mL/kg body weight) and 90-180 µm PVA particles. After embolization, the animals in each subgroup were sacrificed at 6 hours, 24 hours, and 3 days, and the tumor samples were collected. Immunohistochemical staining was performed to evaluate expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins, and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels.

Results: The levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P<0.05). There was a slight decrease in tumor size in the liposomal curcumin TAE-treated group at third-day time points compared to the TAE-treated group; the difference was not statistically significant (P>0.05). The HIF-1α protein correlated considerably with VEGF mRNA (r=0.705, P=0.001) and protein (r=0.655, P=0.003), and MVD (r=0.521, P=0.027). A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).

Conclusion: Liposomal curcumin downregulates HIF-1α protein levels and inhibits hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining of VEGF.Notes: (A and B) Control group: tumors showed scattered VEGF-positive cells (arrows), (A: ×200, B: ×400). (C and D) TAE-treated group: much more VEGF-positive expression showed in the tumors, which demonstrated a 3+ staining (arrows) (C: ×200, D: ×400). (E and F) Liposomal curcumin TAE-treated group: VEGF-positive tumor cells decreased compared with TAE group, which demonstrated a 1+ staining (arrows) (E: ×200, F: ×400).Abbreviations: VEGF, vascular endothelial growth factor; TAE, transcatheter arterial embolization; N, necrosis.
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f5-ott-8-2601: Immunohistochemical staining of VEGF.Notes: (A and B) Control group: tumors showed scattered VEGF-positive cells (arrows), (A: ×200, B: ×400). (C and D) TAE-treated group: much more VEGF-positive expression showed in the tumors, which demonstrated a 3+ staining (arrows) (C: ×200, D: ×400). (E and F) Liposomal curcumin TAE-treated group: VEGF-positive tumor cells decreased compared with TAE group, which demonstrated a 1+ staining (arrows) (E: ×200, F: ×400).Abbreviations: VEGF, vascular endothelial growth factor; TAE, transcatheter arterial embolization; N, necrosis.

Mentions: For VEGF, positivity was indicated as a cytoplasmic expression. Compared to the other groups, representative VEGF-positive cells were highly presented in the residual tumors near necrosis zone in the TAE-treated group (Figure 5). The levels of VEGF mRNA and protein substantially decreased and had a statistical difference at three time points (P<0.05) in the liposomal curcumin TAE-treated tumors compared with the TAE-treated tumors (Figure 6 and Table 2). However, no significant difference was found in VEGF levels between the control group and the liposomal curcumin TAE-treated group (P>0.05) (Table 2).


Liposomal curcumin inhibits hypoxia-induced angiogenesis after transcatheter arterial embolization in VX2 rabbit liver tumors.

Dai F, Zhang X, Shen W, Chen J, Liu L, Gao G - Onco Targets Ther (2015)

Immunohistochemical staining of VEGF.Notes: (A and B) Control group: tumors showed scattered VEGF-positive cells (arrows), (A: ×200, B: ×400). (C and D) TAE-treated group: much more VEGF-positive expression showed in the tumors, which demonstrated a 3+ staining (arrows) (C: ×200, D: ×400). (E and F) Liposomal curcumin TAE-treated group: VEGF-positive tumor cells decreased compared with TAE group, which demonstrated a 1+ staining (arrows) (E: ×200, F: ×400).Abbreviations: VEGF, vascular endothelial growth factor; TAE, transcatheter arterial embolization; N, necrosis.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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f5-ott-8-2601: Immunohistochemical staining of VEGF.Notes: (A and B) Control group: tumors showed scattered VEGF-positive cells (arrows), (A: ×200, B: ×400). (C and D) TAE-treated group: much more VEGF-positive expression showed in the tumors, which demonstrated a 3+ staining (arrows) (C: ×200, D: ×400). (E and F) Liposomal curcumin TAE-treated group: VEGF-positive tumor cells decreased compared with TAE group, which demonstrated a 1+ staining (arrows) (E: ×200, F: ×400).Abbreviations: VEGF, vascular endothelial growth factor; TAE, transcatheter arterial embolization; N, necrosis.
Mentions: For VEGF, positivity was indicated as a cytoplasmic expression. Compared to the other groups, representative VEGF-positive cells were highly presented in the residual tumors near necrosis zone in the TAE-treated group (Figure 5). The levels of VEGF mRNA and protein substantially decreased and had a statistical difference at three time points (P<0.05) in the liposomal curcumin TAE-treated tumors compared with the TAE-treated tumors (Figure 6 and Table 2). However, no significant difference was found in VEGF levels between the control group and the liposomal curcumin TAE-treated group (P>0.05) (Table 2).

Bottom Line: The levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P<0.05).There was a slight decrease in tumor size in the liposomal curcumin TAE-treated group at third-day time points compared to the TAE-treated group; the difference was not statistically significant (P>0.05).A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).

View Article: PubMed Central - PubMed

Affiliation: The First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China ; Department of Interventional Radiology, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, People's Republic of China.

ABSTRACT

Purpose: The purpose of the study is to investigate the inhibition of hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors by liposomal curcumin.

Materials and methods: A total of 54 VX2 rabbits were divided into three groups, and each group had three subgroups according to the sacrifice time. The animals in the control group (n=18) underwent sham embolization. Transcatheter arterial embolization (TAE)-treated group (n=18) animals underwent embolization with lipiodol (0.1 mL/kg body weight) and 90-180 µm polyvinyl alcohol (PVA) particles. Liposomal curcumin TAE-treated group (n=18) animals underwent embolization with liposomal curcumin (20 mg/kg body weight) mixed with lipiodol (0.1 mL/kg body weight) and 90-180 µm PVA particles. After embolization, the animals in each subgroup were sacrificed at 6 hours, 24 hours, and 3 days, and the tumor samples were collected. Immunohistochemical staining was performed to evaluate expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins, and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels.

Results: The levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P<0.05). There was a slight decrease in tumor size in the liposomal curcumin TAE-treated group at third-day time points compared to the TAE-treated group; the difference was not statistically significant (P>0.05). The HIF-1α protein correlated considerably with VEGF mRNA (r=0.705, P=0.001) and protein (r=0.655, P=0.003), and MVD (r=0.521, P=0.027). A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).

Conclusion: Liposomal curcumin downregulates HIF-1α protein levels and inhibits hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors.

No MeSH data available.


Related in: MedlinePlus