The Radiosensitization Enhancement Of A Selective Cyclooxygenase-2 Inhibitor In Lung Cancer Cell Line(A549) And Its Possible Mechanisms.

Object:To investigate the enhancement of radiosensitization of COX-2 inhibitor Nimesuilide on lung cancer cell line in viro and try to research the possible radiosensitizing mechanisms.Methods:The A549 cell line were divided into four group:(1)the control: without Nimesuilide and radiation interference;(2)radiation alone: X-ray at a dose of 2,4,6or 8Gy, respectively;(3) Nimesuilide alone: Nimesuilide 25μmol/l exposed to A549 for 24h; (4) Nimesuilide and radiation :after 25μmol/l Nimesuilide exposed to A549 cell for 24h,X-ray was given at a dose of 2,4,6,8 respectively. The cell proliferation inhibitory effects of different dosages of Nimesuilide on A549 cells was detected by MTT assay.The change in radiosensitivity was quantified by calculating the sensitization enhancement radio at a clinically relevant dose of 2Gy(SERSF2 ) by clonogenic assay. Cell cycle in different groups were detected by flow cytometry(FCM). Flow cytometry detected the contents of Bcl-2 and Bax.;the percentages of apoptosis in each group .Results: Nimesuilide can inhibit the growth of A549cells .The A549 inhibition effect was positively related with the time and concentration of drug treatment by MTT. By simulating the survival curve with the model of muti-target and single-split, the D0,Dq,SF2 of A549 cell for radiation alone were 3.28±0.05,2.09±0.18,0.81±0.04, respectively. The group of Nimesuilide combined with radiation were 2.38±0.08,0.43±0.01,0.51±0.04 ,respectively. The percentage of cells in Go/G1,S,G2/M cell cycle phase in control were 60.01±1.86,24.33±1.30,15.88±2.05, respectively. The group of Nimesuilide alone were 78.24±2.05 14.25±1.47 7.62±1.72.The difference was significant. Nimesuilide combined with X-ray could up-regulate of the protein of Bax, inhibit the expression of Bcl-2 and increase the apoptosis rate of A549 cell.Conclusion: Our results demonstrated that Nimesuilide enhanced the radiosensitivity of lung cancer cell line(A549)in a dose-dependent. The mechanism of radiosensitization was possibly associated with G2/M arrest. Nimesuilide combined with X-ray can up-regulate of the protein of Bax, inhibit the expression of Bcl-2 and increase the apoptosis of A549 cell.