Effect Of All-trans Retinoic Acid On Radiosensitivity Of Lung Cancer Cell Line A549

Objective: To investigate the radiosensitive effect of all-trans retinoicacid(ATRA) on lung cancer cell line A549cultured in vitro and its possiblemechanism.Methods: The A549cells in the logarithmic growth phase weredivided into four groups: control group, ATRA group, radiation group,combination group(ATRA combined with radiation). MTT assay was usedto detect the growth inhibition rate and to further filter out the bestexperimental concentration of ATRA. The radiosensitive effect wasdetected by clone formation test. The cell cycle and apoptosis wasmeasured by flow cytometry. The expression of VEGF mRNA was detectedby reverse transcription polymerase chain reaction(PT-PCR). The VEGFvalues in the cell supernatant were detected by ELISA.Results:1. ATRA could inhibit the proliferation of A549cells, and showed atime and dose dependent. The optimal dose of ATRA was10umol/L.2. The value of SF2、N、D0、Dq were significantly decreased incombination group compared with those in radiation group（0.889vs0.82、 4.157vs3.953、3.432vs2.449、2.283vs1.858，P＜0.05）. To a certainextent, ATRA can enhance the radiosensitivity of A549cells.3. The proportion of G0/G1phase in ATRA group was significantlyincreased compared with that in control group ［(56.45±1.26)%vs(47.88±1.04)%，P＜0.05］. The proportion of G2/M phase in radiation groupwas significantly increased compared with that in control group［(33.89±1.24)%vs (24.75±0.85)%，P＜0.05］.4. The apoptosis rate in combination group was significantly increasedcompared with that in ATRA group and radiation group［(25.17±0.81)%vs(15.64±0.73)%，(25.17±0.81)%vs (18.01±1.05)%，P＜0.05］. As comparedwith the apoptosis rate of the control group，that of the ATRA group, theradiation group and the combination group increased significantly［(15.64±0.73)%、(18.01±1.05)%、(25.17±0.81)%vs (7.63±0.52)%，P＜0.05］.5. The expressions of VEGF mRNA were significantly reduced inATRA group compared with those in control group（1.329±0.027vs1.685±0.031， P＜0.05）. The expressions of VEGF mRNA weresignificantly increased in radiation group compared with those in controlgroup（1.834±0.042vs1.685±0.031，P＜0.05）.The expressions of VEGFmRNA were significantly decreased in combination group compared withthose in radiation group（1.517±0.034vs1.834±0.042，P＜0.05）.6. The VEGF levels in the supernatant of ATRA group were significantly decreased compared with those in control group （P＜0.05）.The VEGF levels in the supernatant of radiation group weresignificantly increased compared with those in control group（P＜0.05）.The VEGF levels in the supernatant of combination group weresignificantly reduced compared with those in radiation group（P＜0.05）.Conclusion: All-trans retinoic acid can increase the radiosensitivity ofA549cells. The mechanism may be related with the direct inhibition ofATRA on A549cells, inducement of the apoptosis and down-regulation ofthe expression of VEGF in tumor cells.