GDC-0980-induced apoptosis is enhanced by autophagy inhibition in human pancreatic cancer cells

2014 ◽  
Vol 453 (3) ◽  
pp. 533-538 ◽  
Author(s):  
Jian-ying Tang ◽  
Tu Dai ◽  
Hui Zhang ◽  
Wu-jun Xiong ◽  
Ming-zheng Xu ◽  
...  
2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Eun Kyoung Jeon ◽  
Young Seon Hong

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.


1999 ◽  
Vol 83 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Theodore P. McDade ◽  
Richard A. Perugini ◽  
Frank J. Vittimberga ◽  
Rebecca C. Carrigan ◽  
Mark P. Callery

2013 ◽  
Vol 105 (9) ◽  
pp. 414-429 ◽  
Author(s):  
Reka Chakravarthy ◽  
Michael J. Clemens ◽  
Grisha Pirianov ◽  
Nectarios Perdios ◽  
Satvinder Mudan ◽  
...  

Oncogene ◽  
2003 ◽  
Vol 22 (14) ◽  
pp. 2088-2096 ◽  
Author(s):  
Hao Zhang ◽  
Takashi Morisaki ◽  
Chihiro Nakahara ◽  
Hisashi Matsunaga ◽  
Noshiro Sato ◽  
...  

2011 ◽  
Vol 140 (5) ◽  
pp. S-684
Author(s):  
Hiroki Takahashi ◽  
Monica C. Chen ◽  
Diane M. Harris ◽  
Hung Pham ◽  
Howard A. Reber ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0127386 ◽  
Author(s):  
Min Zhang ◽  
Nanae Harashima ◽  
Tamami Moritani ◽  
Weidong Huang ◽  
Mamoru Harada

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