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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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Lipo-cur inhibits radiation-inducing fibrosis in C57 mice. (A) Picric Acid-Sirius Red staining of lung tissue. Sections of the lung from radiated C57 mice at 3, 4, 5, and 6 weeks were analyzed for interstitial collagen content by Picric Acid-Sirius Red staining. Magnification: ×100. (B) Quantification of lung fibrosis by Sirius Red staining and subsequent semi-automated image analysis. Data are from two representative lung sections per animal from three different animals per group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.01 between groups.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; w, week.
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f4-ijn-7-2601: Lipo-cur inhibits radiation-inducing fibrosis in C57 mice. (A) Picric Acid-Sirius Red staining of lung tissue. Sections of the lung from radiated C57 mice at 3, 4, 5, and 6 weeks were analyzed for interstitial collagen content by Picric Acid-Sirius Red staining. Magnification: ×100. (B) Quantification of lung fibrosis by Sirius Red staining and subsequent semi-automated image analysis. Data are from two representative lung sections per animal from three different animals per group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.01 between groups.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; w, week.

Mentions: Lungs were analyzed at 7, 14, 21, 28, 35, and 42 days for the onset of the pneumonitis reaction. Histopathologic changes were judged by two independent investigators in a blinded manner. These results revealed that radiation once with 14 Gy lead to an increase in acute inflammatory infiltrate in the interstitium. The mice from the control group developed pathognomonic alterations characteristic of pneumonitis, including alveolar wall thickness, interstitial edema, and interstitial and peribronchial inflammation after radiation. However, the lung tissue from the Lipo-cur-treated group only showed slight histopathologic changes during the 6 weeks (Figure 3A). The murine lung inflammation from the control group had further developed until progressive fibrosis of interstitium, while the systemic and repeated administration of Lipo-cur not only inhibited the onset of RP, but also retarded its process and sequelae (Figure 3B). The degree of type I collagen deposition was confirmed by lung histology stained with Picric Acid-Sirius Red (Figure 4A). As anticipated, lung tissue specimens from the empty liposome group showed extensive Picric Acid-Sirius Red staining, indicating type I collagen deposition inside the alveolar wall. This suggested that the degree of lung fibrosis in the control group significantly increased compared with that in the Lipo-cur- treated group (P < 0.01) (Figure 4B).


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)

Lipo-cur inhibits radiation-inducing fibrosis in C57 mice. (A) Picric Acid-Sirius Red staining of lung tissue. Sections of the lung from radiated C57 mice at 3, 4, 5, and 6 weeks were analyzed for interstitial collagen content by Picric Acid-Sirius Red staining. Magnification: ×100. (B) Quantification of lung fibrosis by Sirius Red staining and subsequent semi-automated image analysis. Data are from two representative lung sections per animal from three different animals per group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.01 between groups.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; w, week.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368513&req=5

f4-ijn-7-2601: Lipo-cur inhibits radiation-inducing fibrosis in C57 mice. (A) Picric Acid-Sirius Red staining of lung tissue. Sections of the lung from radiated C57 mice at 3, 4, 5, and 6 weeks were analyzed for interstitial collagen content by Picric Acid-Sirius Red staining. Magnification: ×100. (B) Quantification of lung fibrosis by Sirius Red staining and subsequent semi-automated image analysis. Data are from two representative lung sections per animal from three different animals per group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.01 between groups.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; w, week.
Mentions: Lungs were analyzed at 7, 14, 21, 28, 35, and 42 days for the onset of the pneumonitis reaction. Histopathologic changes were judged by two independent investigators in a blinded manner. These results revealed that radiation once with 14 Gy lead to an increase in acute inflammatory infiltrate in the interstitium. The mice from the control group developed pathognomonic alterations characteristic of pneumonitis, including alveolar wall thickness, interstitial edema, and interstitial and peribronchial inflammation after radiation. However, the lung tissue from the Lipo-cur-treated group only showed slight histopathologic changes during the 6 weeks (Figure 3A). The murine lung inflammation from the control group had further developed until progressive fibrosis of interstitium, while the systemic and repeated administration of Lipo-cur not only inhibited the onset of RP, but also retarded its process and sequelae (Figure 3B). The degree of type I collagen deposition was confirmed by lung histology stained with Picric Acid-Sirius Red (Figure 4A). As anticipated, lung tissue specimens from the empty liposome group showed extensive Picric Acid-Sirius Red staining, indicating type I collagen deposition inside the alveolar wall. This suggested that the degree of lung fibrosis in the control group significantly increased compared with that in the Lipo-cur- treated group (P < 0.01) (Figure 4B).

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