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A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation.

Shi HS, Gao X, Li D, Zhang QW, Wang YS, Zheng Y, Cai LL, Zhong RM, Rui A, Li ZY, Zheng H, Chen XC, Chen LJ - Int J Nanomedicine (2012)

Bottom Line: The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model.The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation.This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

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Inhibition of angiogenesis within tumors. (A and B) Frozen sections of tumor tissue were tested by immunohistochemical analysis of anti-CD31 antibody, and vascular density was quantified by counting the number of microvessels per high power field (×400). Vessel density of tumor tissues from combined treatment with Lipo-cur and RT indicated a decrease compared with the phosphate-buffered saline group (five high power fields per slide). (C and D) Alginate beads containing 1 × 105 LL/2 cells per bead were then implanted subcutaneously into the backs of mice. One group was treated with curcumin by intravenous injection once a day for 1 week, and one group was treated with normal saline. Beads were surgically removed 12 days later, and FITC-dextran was quantified. FITC-dextran uptake of beads from curcumin-treated mice showed a significant decrease compared with normal saline group.Notes: *Denotes P < 0.05; **denotes P < 0.01; columns, mean; bars, standard deviations.Abbreviations: FITC, fluorescein isothiocyanate; Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy.
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f7-ijn-7-2601: Inhibition of angiogenesis within tumors. (A and B) Frozen sections of tumor tissue were tested by immunohistochemical analysis of anti-CD31 antibody, and vascular density was quantified by counting the number of microvessels per high power field (×400). Vessel density of tumor tissues from combined treatment with Lipo-cur and RT indicated a decrease compared with the phosphate-buffered saline group (five high power fields per slide). (C and D) Alginate beads containing 1 × 105 LL/2 cells per bead were then implanted subcutaneously into the backs of mice. One group was treated with curcumin by intravenous injection once a day for 1 week, and one group was treated with normal saline. Beads were surgically removed 12 days later, and FITC-dextran was quantified. FITC-dextran uptake of beads from curcumin-treated mice showed a significant decrease compared with normal saline group.Notes: *Denotes P < 0.05; **denotes P < 0.01; columns, mean; bars, standard deviations.Abbreviations: FITC, fluorescein isothiocyanate; Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy.

Mentions: A previous study indicates that irradiation induces endothelial cell apoptosis and resulting microvascular damage regulates tumor cell response to radiation.34 Accumulating evidence have been documented that curcumin inhibits angiogenesis by targeting endothelial cells.35–37 In this study, immunohistochemical staining (Figure 7A) of the tumor tissue from curcumin-treated mice with an anti-CD31 antibody showed significantly decreased microvessel density compared with that of the empty liposome group. Interestingly, the microvessels were still obviously observed in tumor tissue from single irradiation-treated mice; however, both the microvessels and cancer cells showed morphologic abnormality, suggesting the damages and disfunction of these microvessels. The combined treatment with Lipo-cur plus radiotherapy resulted in significantly decreased microvessels (Figure 7A and B). In addition, inhibition of angiogenesis could also be detected in the alginate-encapsulate tumor cell assay (Figure 7C and D). New blood vessels in alginate beads from curcumin therapic mice were apparently sparse. Besides, FITC-dextran uptake was significantly decreased from Lipo-cur-treated mice. These findings further support that curcumin effectively inhibits tumor angiogenesis; it is a possible mechanism to sensitize LL/2 Lewis lung carcinoma cells to radiotherapy.


A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation.

Shi HS, Gao X, Li D, Zhang QW, Wang YS, Zheng Y, Cai LL, Zhong RM, Rui A, Li ZY, Zheng H, Chen XC, Chen LJ - Int J Nanomedicine (2012)

Inhibition of angiogenesis within tumors. (A and B) Frozen sections of tumor tissue were tested by immunohistochemical analysis of anti-CD31 antibody, and vascular density was quantified by counting the number of microvessels per high power field (×400). Vessel density of tumor tissues from combined treatment with Lipo-cur and RT indicated a decrease compared with the phosphate-buffered saline group (five high power fields per slide). (C and D) Alginate beads containing 1 × 105 LL/2 cells per bead were then implanted subcutaneously into the backs of mice. One group was treated with curcumin by intravenous injection once a day for 1 week, and one group was treated with normal saline. Beads were surgically removed 12 days later, and FITC-dextran was quantified. FITC-dextran uptake of beads from curcumin-treated mice showed a significant decrease compared with normal saline group.Notes: *Denotes P < 0.05; **denotes P < 0.01; columns, mean; bars, standard deviations.Abbreviations: FITC, fluorescein isothiocyanate; Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368513&req=5

f7-ijn-7-2601: Inhibition of angiogenesis within tumors. (A and B) Frozen sections of tumor tissue were tested by immunohistochemical analysis of anti-CD31 antibody, and vascular density was quantified by counting the number of microvessels per high power field (×400). Vessel density of tumor tissues from combined treatment with Lipo-cur and RT indicated a decrease compared with the phosphate-buffered saline group (five high power fields per slide). (C and D) Alginate beads containing 1 × 105 LL/2 cells per bead were then implanted subcutaneously into the backs of mice. One group was treated with curcumin by intravenous injection once a day for 1 week, and one group was treated with normal saline. Beads were surgically removed 12 days later, and FITC-dextran was quantified. FITC-dextran uptake of beads from curcumin-treated mice showed a significant decrease compared with normal saline group.Notes: *Denotes P < 0.05; **denotes P < 0.01; columns, mean; bars, standard deviations.Abbreviations: FITC, fluorescein isothiocyanate; Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy.
Mentions: A previous study indicates that irradiation induces endothelial cell apoptosis and resulting microvascular damage regulates tumor cell response to radiation.34 Accumulating evidence have been documented that curcumin inhibits angiogenesis by targeting endothelial cells.35–37 In this study, immunohistochemical staining (Figure 7A) of the tumor tissue from curcumin-treated mice with an anti-CD31 antibody showed significantly decreased microvessel density compared with that of the empty liposome group. Interestingly, the microvessels were still obviously observed in tumor tissue from single irradiation-treated mice; however, both the microvessels and cancer cells showed morphologic abnormality, suggesting the damages and disfunction of these microvessels. The combined treatment with Lipo-cur plus radiotherapy resulted in significantly decreased microvessels (Figure 7A and B). In addition, inhibition of angiogenesis could also be detected in the alginate-encapsulate tumor cell assay (Figure 7C and D). New blood vessels in alginate beads from curcumin therapic mice were apparently sparse. Besides, FITC-dextran uptake was significantly decreased from Lipo-cur-treated mice. These findings further support that curcumin effectively inhibits tumor angiogenesis; it is a possible mechanism to sensitize LL/2 Lewis lung carcinoma cells to radiotherapy.

Bottom Line: The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model.The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation.This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

Show MeSH
Related in: MedlinePlus