Huang Xiaolong,Zhang Hao,Xie Xiangyu,Yang Xiaoyu,He Weiyang.Gemcitabine induces autophagy in human bladder cancer T24 cells[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(01):9-15.
Huang Xiaolong,Zhang Hao,Xie Xiangyu,Yang Xiaoyu,He Weiyang.Gemcitabine induces autophagy in human bladder cancer T24 cells[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(01):9-15.DOI:
Objective To investigate whether gemcitabine (GEM) will activate autophagy when GEM induced apoptosis in human bladder cancer T24 cells
and explore the underlying mechanism and the relationship between autophagy and apoptosis induced by GEM. Methods Cell counting kit-8 (CCK-8) assay was used to detect the growth inhibition in human bladder cancer T24 cells after GEM treatment. Western blotting was used to detect the apoptosis related proteins Caspase-3 and PARP
autophagy marker proteins LC3-Ⅱ
P62 and autophagy flux
and JNK signaling pathway related proteins Jnk1
PJnk and Bcl-2. Transmission electron microscopy (TEM) was employed to observe the intracellular autophagosome. Flow cytometry (FCM) was used to measure cell apoptosis with aid of Annexin V-FITC apoptosis detection kit after inhibition of autophagy. Results CCK-8 assay revealed that GEM effectively inhibited the proliferation of T24 cells. GEM treatment of 1.0 μg/mL resulted in obvious autophagy in the cells
and TEM displayed the formation of intracellular autophagosome. The results Western blotting showed the expression levels of cleaved-Caspase-3
PARP and LC3-Ⅱ were elevated
while that of p62 was reduced after GEM treatment. GEM also phosphorylated JNK and suppressed Bcl-2 to activate JNK signaling pathway. Inhibition of autophagy could enhance cell apoptosis in T24 cells after GEM treatment. Conclusion GEM induces cell apoptosis in T24 cells
and also induces autophagy to protect the cells against apoptosis at the same time. JNK signaling pathway is involved in the regulation of autophagy
and inhibition of autophagy will significantly enhance the chemosensitivity of T24 cells to GEM.