Effects Of Fentanyl And Remifentanil On Viability Of Human Lung Cancer Cell Line A549

Objective:Lung cancer is a common respiratory tract malignancy which can be treated by surgical resection and causes severe pain for terminal cancer patients.Opioid analgesics are widely used in cancerous patient operation, postoperative analgesia, and treatment of cancer pain. Opioid analgesics, with the analgesic effect,doesn’t show whether they have impact on the growth of cancer cells,and whether they promote or inhibit the growth and reproduction of cancer cells is not clear.The study investigated the effects of fentanyl and remifentanil on viability of human lung cancer cell line A549to provide a reference for the clinical application.Methods:Human lung cancer A549cells were cultured to logarithmic phase and were seeded in75ml culture bottles or96-well plates.After being cultured for24h,the cells were randomly divided into9groups:group I normal control(group C),group Ⅱ-Ⅴ were exposed to fentanyl0.5,5,50and500ng/ml respectively(group F1-F4),groupⅥ-Ⅸ were exposed to remifentanil0.5,5,50and500ng/ml respectively(group RF1-RF4).The viability of the cells were determined by MTT assay after being incubated with fentanyl or remifentanil for24,48and72h.The apoptosis rates and cell cycle distribution were determined by flow cytometry after being incubated with fentanyl or remifentanil for24h.Results:1Vitality of nine group A549cells at different incubation time points:The viability of nine group A549cells was no significant difference at being cultured24,48h respectively(P>0.05).Compared with group C,the viability of the cells was no significant difference in groups F1and RFlat being cultured72h(P>0.05).The growth and proliferation of A549cells were inhibited after fentanyl applied and the mean proliferation rates of A549cells in groups F2-F4were(0.701±0.045)%,(0.523±0.057)%,(0.407±0.062)%,which were lower than the control cells(1.012±0.173)%(P<0.05).The mean proliferation rates of A549cells in groups RF2-RF4were(0.758±0.082)%,(0.501±0.102)%,(0.399±0.075)%,which were lower than the control cells(1.012±0.173)%(P<0.05).Compared with group C,the viability of the cells at being cultured72h were significantly decreased in a dose-independent manner in groups F2-F4and RF2-RF4(P<0.05).2The apoptosis rates of nine group A549cells:Compared with group C,the apoptosis rates were no significant difference in groups F1and RF1(P>0.05). The apoptosis rates of A549cells in groups F2-F4were(9.4±1.9)%,(16.9±2.1)%,(25.1±3.7)%,which were lower than the control cells(3.7±1.7)%(P<0.05).The apoptosis rates of A549cells in groups RF2-RF4were(9.6±1.5)%,(17.1±2.3)%,(23.8±4.9)%,which were lower than the control cells(3.7±1.7)%(P<0.05).Compared with group C,the apoptosis rates of A549cells were increased in a dose-independent manner in groups F2-F4and RF2-RF4(P<0.05).3The cell cycle distribution of nine group A549cells:The proportions in S phase in groups F2-F4were(35±4)%,(30±5)%,(24±3)%,which were lower than the control group C(40±5)%;however,the proportions in G2/M phase in groups F2-F4were(8.40±1.02)%,(13.12±2.05)%,(18.21±2.73)%,which were higher than the control group C(1.38±0.13)%(P<0.05).The proportions in S phase in groups RF2-RF4were(35±5)%,(30±7)%,(25±4)%,which were lower than the control group C(40±5)%;however,the proportions in G2/M phase in groups RF2-RF4were(7.82±1.07)%,(12.15±2.13)%,(18.09±2.87)%,which were higher than the control group C(1.38±0.13)%(P<0.05).Compared with group C,the proportions of the cells in S phase were decreased,while the proportions of the cells in G2/M phase were significantly increased in a dose-independent manner in groups F2-F4and RF2-RF4(P<0.05).4There was no significant difference between groups equal dose fentanyl and remifentanil(P>0.05).Conclusion:Fentanyl and remifentanil (concentration≥5ng/ml)can inhibit the viability of human lung cancer cells in a dose-independent manner by its apoptosis inducing effects and make cell cycle arrest in G2/M phase.