Gefitinib does not enhance radiation caused lung injury in vivo / 中华放射肿瘤学杂志

ABSTRACT

ObjectiveTo evaluate the effect on lung injury of gefitinib or/and radiation.Methods Totally 160 mice were divided into five groups:control (C) ;gefitinib (G) ;radiation (R) ;gefitinib followed by irradiation ( G + R) ;and R + G.12 Gy irradiation was delivered.Geiitinib fed by 200 mg/kg once daily for 3 weeks.Mice were sacrificed on 1,2,4 or 6 months after radiation.Macrophage count of lung lavage fluid and hydroxyproline assessed,lung fibrosis scored.and plasma TGF-β1 concentration assayed.One-way ANOVA was used to test the significance. Results The lung lavage macrophage cell number were significantly higher in group R,R + G and G + R than group C ( q =2.95 - 8.61,all P ＜ 0.05 ) on 4 and 6months,yet no significant difference between the three groups ( q =0.37 -3.49,all P ＜ 0.05 ) ; The macrophage was significantly lower in month 1,4 and 6 in group G than R,R + G and G + R ( q =3.37- 6.25,all P ＜ 0.05 ).The hydroxyproline content and the fibrosis score of G,R,R + G and G + R were significantly higher than C ( q =3.14 - 4.76,all P ＜ 0.05 ),but no significant difference between the four groups ( q =0.70 - 4.19,all P ＞ 0.05 ).The TGF-β1 concentration of R,G + R,R + G at all time points and TGF-β1 concentration of G at 1 st and 2nd months were significantly higher than C ( q =3.76 -8.09,all P ＜ 0.05).ConclusionsGefitinib could cause lung fibrosis in vivo in BalB/C mouse.The combination of gefitinib and radiation did not significantly exacerbate lung injury caused byeither alone.The mechanism of lung fibrosis caused by gefitinib might be different from that by radiation which needs further research.