Abstract Objective To observe the effects of pigment epithelium-derived factor (PEDF) on vascular normalization in lung cancer and further investigate the combined effects of PEDF and radiation on the growth of lung cancer. Methods Immunofluorescent staining was used to observe the effects of PEDF on vascular normalization in lung cancer and determine the time window of vascular normalization. C57BL/6 mice bearing Lewis lung carcinoma xenografts were prepared and divided into control group, PEDF group,radiation group, and PEDF+radiation groups. The growth of tumor xenografts was evaluated. ResultsPEDF reduced the vascular density and basement membrane thickness of Lewis lung carcinoma xenografts, increased the pericyte coverage of blood vessels, and reduced the hypoxic fraction of tumor xenografts. On days 3-7 of PEDF treatment, the PEDF group had a reduced fraction of hypoxic tumor cells compared with the control group (33.73%), and the lowest value for PEDF group was seen on day 3(20.79%). The time window of vascular normalization induced by PEDF was days 3-7. PEDF combined with radiation delivered on day 5 of PEDF treatment had a stronger inhibitory effect on tumor xenografts than radiation alone and PEDF combined with radiation delivered on day 1 of PEDF treatment. Conclusions PEDF can promote the vascular normalization in lung cancer and enhance the anti-lung cancer effect of radiation.
Corresponding Authors:
Chen Ming, Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310012, China;Email:chenmingdr@163.com
Cite this article:
. Pigment epithelium-derived factor enhances radiation response by inducing vascular normalization in Lewis lung carcinoma[J]. Chinese Journal of Radiation Oncology, 2014, 23(5): 448-453.
. Pigment epithelium-derived factor enhances radiation response by inducing vascular normalization in Lewis lung carcinoma[J]. Chinese Journal of Radiation Oncology, 2014, 23(5): 448-453.
[1] Citrin D, Menard C, Camphausen K. Combining radiotherapy and angiogenesis inhibitors:clinical trial design[J]. Int J Radiat Oncol Biol Phys,2006,64:15-25. [2] Jain RK. Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J]. Science,2005,307:58-62. [3] Tombran-Tink J, Chader G G, Johnson L V. PEDF:a pigment epithelium-derived factor with potent neuronal differentiative activity[J]. Exp Eye Res,1991,53:411-414. [4] Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor:a potent inhibitor of angiogenesis[J]. Science,1999,285:245-248. [5] Ek ET, Dass CR, Choong PF. Pigment epithelium-derived factor:a multimodal tumor inhibitor[J]. Mol Cancer Ther,2006,5:1641-1646. [6] Yang H, Cheng R, Liu G, et al. PEDF inhibits growth of retinoblastoma by anti-angiogenic activity[J].Cancer Sci,2009,100:2419-2425. [7] Maione F, Molla F, Meda C, et al. Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models[J]. J Clin Invest,2009,119:3356-3372. [8] Huang G, Chen L. Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma[J]. J Cancer Res Clin Oncol,2010,136:1201-1211. [9] Li N, Zheng D, Wei X, et al. Effects of recombinant human endostatin and its synergy with cisplatin on circulating endothelial cells and tumor vascular normalization in A549 xenograft murine model[J]. J Cancer Res Clin Oncol,2012,138:1131-1144. [10] Peng F, Xu Z, Wang J, et al. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models[J/OL]. PLoS One,2012,7(4):e34646[2013-11-12]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322143/. [11] Jin GH, Ma DY, Wu N, et al. Combination of human plasminogen kringle 5 with ionizing radiation significantly enhances the efficacy of antitumor effect[J]. Int J Cancer,2007,121:2539-2546. [12] Xu Z, Fang S, Zuo Y, et al. Combination of pigment epithelium-derived factor with radiotherapy enhances the antitumor effects on nasopharyngeal carcinoma by downregulating vascular endothelial growth factor expression and angiogenesis[J]. Cancer Sci,2011,102:1789-1798. [13] Kulke MH, Bergsland EK, Ryan DP, et al. Phase Ⅱ study of recombinant human endostatin in patients with advanced neuroendocrine tumors[J]. J Clin Oncol,2006,24:3555-3561. [14] 韩宝惠,修清玉,王慧敏,等.紫杉醇卡铂联合重组人血管内皮抑制素注射液治疗晚期非小细胞肺癌的疗效及生活质量分析[J].中华肿瘤杂志,2011,33:854-859. [15] Zhou ZT, Zhou FX, Wei Q, et al. Phase Ⅱ study of cisplatin/etoposide and endostar for extensive-stage small-cell lung cancer[J]. Cancer Chemother Pharmacol,2011,68:1027-1032. [16] Ge W, Cao DD, Wang HM, et al. Endostar combined with chemotherapy versus chemotherapy alone for advanced NSCLCs:a meta-analysis[J]. Asian Pac J Cancer Prev,2011,12:2705-2711.
2014, Vol. 23 
