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Archive > Volume 20 Issue 2 > 2013,20(2):159-165. DOI:10.3872/j.issn.1007-385X.2013.02.005 Prev Next
Basic Research
Possible mechanism and effect of VEGF on the canceration of ulcerative colitis
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Abstract:
Objective: To investigate the role and mechanism of vascular endothelial growth factor (VEGF) signaling in the development of ulcerative colitis (UC)-related cancer. Methods: Colitis-associated colorectal cancer (CAC) model was established in Balb/c mice. The proportion of myeloid-derived suppressor cells (MDSCs) in the peripheral blood, spleen, bone marrow and tumor tissues of the model mice and lesions was examined by flow cytometry. Arginase-1 (Arg-1) mRNA and inducible nitric oxide synthase (iNOS) mRNA expressions in MDSCs were detected by qPCR. The VEGF expression in the supernatants of colonic tissues was determined by ELISA. Sorafenib or neutralizing anti-VEGF antibody was used to block VEGF signaling and the proportion of MDSC in colonic lesions and the histopathology of CAC were detected. Results: Murine CAC model was established successfully. 1 month and 3 months after the beginning of CAC were verified as the early and late stages of CAC respectively, according to several parameters. The increased number of Gr-1+CD11b+MDSC was observed in the progression of CAC and was more significant in lesions: control (0.30±018)%, early stage of CAC (1.32±0.04)%, late stage of CAC (3.08±0.29)% (P<0.05). These MDSCs expressed a high level of Arg-1 and iNOS (P<0.05). But the levels of L-arginine in colonic lesions of CAC mice was much lower than controls (early stage of CAC \[4.22±0.17\] μg/ml, late stage of CAC \[2.95±1.08\] μg/ml, control \[4.41±0.16\] μg/ml, P<0.05). Furthermore, VEGF expression in the lesions of CAC mice was elevated significantly (early stage of CAC \[1170±94.43\] pg/ml, late stage of \[1117±71.92\] pg/ml, control \[877.6±31.67\] pg/ml, P<0.05). The treatment of sorafenib or anti-VEGF dramatically reduced accumulation of MDSC in the lesions. Conclusion: VEGF plays a pro-tumor role in CAC formation, which may be related with the induced accumulation of MDSC in colonic tissues.
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Project Supported:
Project supported by the National Key Basic Research and Development Project (973 Project) of China (No. 2007CB512406), and the National Natural Science Foundation of China (No. 30801029，No. 81272320)
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