[The effect of Ixabepilone on NSCLC cells radio-sensitivity under quiescent or hypoxic condition]
1Department of Radiotherapy of Huadong Hospital, Shanghai 200040, China.
Objective:
To evaluate the effect of Ixabepilone on quiescent or hypoxic cells response to ionizing radiation.
Methods:
NCI-H460 and A549, two human NSCLC cell lines, were employed in this experiment. Quiescent cells (QC) or hypoxic cells (HC) were induced as mentioned previously and untreated cells as control. A colony forming assay was applied to compare cellular radio-sensitivity with or without Ixabepilone. Flow cytometry and Western blot analysis were used to detect cell cycle distribution and apoptosis.
Results:
Along with an increased population of G1 cell (NCI-H46 P=0.001 3; A549 P=0.006), both HC and QC were exhibited radio-resistance compared to untreated cells (survival fraction: NCI-H460 P=0.003; A549 P=0.000 1). Moreover, it was found that Ixabepilone, which induced apoptosis in both IR-treated or untreated NSCLC cells, significantly enhanced cells death under hypoxia (decrease of survival fraction: NCI-H460 P=0.000 2; A549 P<0.01).
Conclusion:
The existence of quiescent or hypoxic cells in solid tumors poses a critical therapeutic problem since they were resistant to IR. Ixabepilone, which induces apoptosis in NSCLC, showed great radio-sensitization effect on hypoxic cells. Following work will focus on whether Ixabepilone could increase hypoxic tumor cells radio-sensitivity in vivo, which could provide useful data for the application of Ixabepilone in clinical practice.
