[Combined effects of endostatin gene transfer and ionizing radiation on lung adenocarcinoma model of A549-cells].

OBJECTIVE

The combined inhibition effects of endostatin gene transfer and ionizing radiation on lung adenocarcinoma model of A549-cell were investigated.

METHODS

Human endostatin gene was transferred into lung adenocarcinoma A549 cell by retrovirus-mediation to obtain an A549/Endo cell. A549 and A549/Endo cells were xenoimplanted in nude mice respectively (each group included 10 mice). Then, the changes of the tumor size of each group (n = 5) and its growth inhibition rate were estimated. The implanted tumors of each group (n = 5) were exposed to radiation with 20 Gy at 28 day after implantation. They were irradiated again with 20 Gy 3 day later. The ionizing radiation was strictly confined to the tumor by shielding the rest of the body with lead. The size of tumor was measured periodically. The microvessel density (MVD) of 4 groups of implanted tumors (A549, A549/Endo, A549 + IR and A549/Endo + IR) were compared on day 42 postgrafting by the immunohistochemical method.

RESULTS

PCR confirmed that endostatin gene was inserted into the genomic DNA of human lung adenocarcinoma A549 cell. The tumor formation time showed significant difference (P < 0.05) between group A549 (7.8 +/- 1.6) d and group A549/Endo (12.2 +/- 1.7) d. At the time of day 42 postgrafting, the tumor sizes of group A549 and group A549/Endo were (927.8 +/- 269.2) mm3 and (217.5 +/- 81.5) mm3 respectively (P < 0.01), and the tumor growth inhibition rate was 76. 5%. At the time of day 14 after irradiation, the tumor sizes of group A549 and group A549/Endo were (157.7 +/- 49.0) mm3 and (4.6 +/- 2.9) mm3 respectively (P < 0.01). The results of immunohistochemical detection showed that the MVD of-A549/Endo implanted tumor was significantly decreased [21.62 +/- 3.55 compared with A549 implanted tumor 35.78 +/- 5.67 (P < 0.01)]. Moreover , it also showed that ionizing radiation could further reduce the MVD of A549/Endo implanted tumor from 21.62 +/- 3.55 to 11.32 +/- 2.78 (P < 0.01).

CONCLUSIONS

Retroviruses can highly mediate the transfer of endostatin gene into the adenocarcinoma cells. Endostatin gene transfer can inhibit the xenoimplanted tumor growth by its direct inhibition on neovascularization. The combination of endostatin gene transfer with ionizing radiation treatment can synergistically inhibit the neovascularization and the growth of lung adenocarcinoma.