Pigment epithelium-derived factor enhances radiation response by inducing vascular normalization in Lewis lung carcinoma

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. Results: PEDF 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. (authors)