A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation.
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.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Hua-shan
HS
Shi
Xiang
X
Gao
Dan
D
Li
Qiong-wen
QW
Zhang
Yong-sheng
YS
Wang
Yu
Y
Zheng
Lu-lu
LL
Cai
Ren-ming
RM
Zhong
Ao
A
Rui
Zhi-yong
ZY
Li
Hao
H
Zheng
Xian-cheng
XC
Chen
Li-juan
LJ
Chen
D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D000077192:Adenocarcinoma of Lung; D000704:Analysis of Variance; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016207:Cytokines / Q000097:blood; D006651:Histocytochemistry; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000532:radiotherapy; D017564:Radiation Pneumonitis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013902:Radiography, Thoracic
D016207:Cytokines; D008081:Liposomes; D011838:Radiation-Sensitizing Agents; D003474:Curcumin