The Features Of Arsenic Trioxides' Selective Effect On The Cell Cycle Of Lung Cancer A549 Cell Line

【Backgrounds and Objective】The case fatality rate of lung cancer is highest among malignant tumor,five-year survial of which is only between 10%and 13%.According to the World Health Organnization prediction:to 2025,the number of lung cancer patients in our country will exceed one millon.The present tragedy of lung cancer is interdiscipline combined therapy, these approaches will attain the goal of therapy through different ways to kill tumor cells, but the consequent is not satisfying.A new direction for tumor treatment is differentiation therapy.The tumor is associated with cell abnormal differentiation,to induce tumor cell differentiation is a new focus on the tumor therapy.Arsenic trioxides(As₂O₃) can induce acute promyelocytic leukemia(APL) into mature granulocytes.The further study has find that it has effect not only on the APL but also on other types of leukemia,even on the solid tumors such as gastric cancer,lung cancer,prostatic carcinoma etal.It inhibits the tumor through influencing the growth and differentiation of tumor cells with different mechanism.Different with other cytotoxic drugs,it can even have apparent inhibitory effect in mionectic tumor tissues.But there has few study about As₂O₃ 's effect on lung cancer cell line in mionectic surroundings.Our objective is to study the features of Arsenic trioxides ' effect on the cell cycle of A549 cell lines in normoxia,explore the influence of hypoxia on the Arsenic trioxides' effect on the cell cycle of A549 cell line.【Materials and Methods】1.Groups of the experiment:there are three cell groups in this study,which comprises 1μmol/L Arsenic trioxides and 1.0μmol/LVP- 16 and the blanket control.2.Cells cultivating:In normoxia microenviroment.theA549 cell lines in are cultivating for 12,24,48hours respectively.In hypoxia and anerobic microenviroment the cell lines are cultivating for 24 hours.3.Collect cells of different groups,and wash them twice with PBS,centrifuge with 1500RPM,fix them with 70%cold alcohol,put them in the refrigerator overnight.4.Dye the cells of different groups with PI solely,then put them in the normal environment for about thirty minutes away from light. 5.Investigate cells DNA contents of different groups respectively through flow cytometry;then analyze the cell cycle and apoptosis results with CellQuest software.6.Analyze the results with SPSS11.0.【Results】1.In normoxia microenvironment,Arsenic Trioxide can prolong A549 G₁ phase rate in cell cycle and decrease A549 S phase rate with the cultivating time increasing,after exploration for about 48 hours,Arsenic groups can make almost half of the cells arresting in the G1 phase,compared with the blanket control groups,the difference is significant (P＜0.05);the S phase cell lines rate is less(P＜0.05).Compared with the VP-16 groups, Arsenic trioxide's effect onf G₁ phase S phase and G₂/M phase is less(P＜0.05),and the apoptosis rate of Arsenic trioxide group is not apparent which is much lower than VP-16 (P＜0.05).2.In hypoxia and anerobic Microenviroment,exploring for 24 hours,the G₁ phase rate is increasing with the severity of oxygen scarcity increasing in three groups;compared with the blanket control groups,the arrest effect on G₁ phase of Arsenic trioxide group is more apparent in anerobic enviroment(P＜0.05),there is no apparent difference between them in nonnoxiaand hypoxia environment.Compared with the VP-16 groups,there are apparent difference between them in three oxygen microenvironment respectively,the G₁ phase and G₂/M phase rate decrease(P＜0.05),and the S phase increase accordingly(P＜0.05).【Conclusion】1.In normoxia microenviroment Arsenic trioxide has a time-dependent effect on the G1 phase arrest to some extent,In hypoxia and anerobic microenviroment,the G1 phase arrest effect of arsenic trioxide.becomes more apparent with the more scarcity of oxygen.but the effect of apoptosis is becoming weaker.2.Low concentration of arsenic trioxide has less apparent effect on A549 cell line cell cycle arrest and apoptosis than VP-16.