title: Protection against acute radiation-induced lung injury: a novel role for the anti-angiogenic agent Endostar.
abstract: Radiotherapy is commonly used to treat thoracic malignancies, but often causes severe lung injury. Currently there are no effective protective strategies against radiation-induced lung injury (RILI). This study aimed to evaluate the ability of an angiogenesis antagonist, Endostar, against RILI, and the underlying mechanism in a mouse model. A total of 108 C57BL/6 female mice were randomized into 4 groups (n=27): i) control group; ii) Endostar group, animals were administered 7.75 ml/kg Endostar through intraperitoneal injection; iii) irradiation group, RILI was induced by exposing the animals to a single external irradiation on the thoraces (6 MV X-ray, 12 Gy); and iv) irradiation plus Endostar group, animals were subjected to Endostar treatment and irradiation as in groups 2 and 3. A total of 3 animals from each of the 4 groups were sacrificed at 1, 6, 12, 24 and 72 h and at 2, 4, 8 and 24 weeks following treatment. Clinical signs and pathology of RILI were examined. The expression of transforming growth factor-β 1 (TGF-β1) in lungs was analyzed by real-time quantitative polymerase chain reaction (RT-QPCR) and immunohistochemistry. Compared with the control group, irradiation induced evident interstitial edema and a significant increase in inflammatory cells in the lungs (P<0.05). Correlated with these changes, a notable increase in TGF-β1 mRNA level and a robust increase in TGF-β1 immunoreactivity were observed in lung tissues in a time-dependent manner following irradiation (P<0.05). Endostar administration effectively attenuated the magnitude of the increase in inflammatory cells as well as the elevation of TGF-β1 expression in lung tissues after RILI (P<0.05). In conclusion, radiation induced an increased expression of the inflammatory mediator TGF-β1 and the associated pathogenesis in the lung, while Endostar was able to at least partially attenuate RILI through downregulating the expression of TGF-β1 in mice. Our findings suggest that Endostar may be a novel protective agent against RILI.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Shenghui
authors.initials: S
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Anwei
authors.initials: A
authors.lastname: Mo
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D043169:Endostatins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011654:Pulmonary Edema / Q000188:drug therapy / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000473:pathology; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D018836:Inflammation Mediators; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; C522911:endostar protein