TY - JOUR
T1 - Inhibition of autophagy potentiates the apoptosis-inducing effects of photodynamic therapy on human colon cancer cells
AU - Ouyang, Guoqing
AU - Xiong, Li
AU - Liu, Zhipeng
AU - Lam, Brandon
AU - Bui, Brian
AU - Ma, Lun
AU - Chen, Xiang
AU - Zhou, Pan
AU - Wang, Kunpeng
AU - Zhang, Zijian
AU - Huang, He
AU - Miao, Xiongying
AU - Chen, Wei
AU - Wen, Yu
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/3
Y1 - 2018/3
N2 - Background: Photodynamic therapy (PDT) has been reported to be a promising therapy for colon cancer because of its substantial safety features and its ability to induce a systematic reaction rather than local effects on the focal lesion in the intestine. Autophagy and apoptosis play important roles in the response to PDT. However, the role of autophagy after PDT treatment has not yet been clarified. Methods: In this study, we investigated the relationship between apoptosis and autophagy in porphyrin IX (PpIX)-mediated PDT (PpIX-PDT) in HCT116 colon cancer cells. PpIX-PDT decreased cell viability in a concentration- and light dose-dependent manner. Results: PpIX-PDT results in nuclear condensation, increased the expression of Caspase-3, Bax, and PARP, and decreased expression of Bcl-2. PpIX-PDT also induces the double membrane autophagosome, up-regulates LC3B, Atg7, Beclin-1, and Bcl-2 expression and down-regulates P62 expression. Inhibition of autophagy using chloroquine (CQ) or Atg7 knockdown with a shRNA enhances apoptotic cell death. Based on these findings, autophagy plays a self-protective role in HCT116 cells in response to PpIX-PDT treatment. Discussion: Both autophagy and apoptosis were induced by PpIX-PDT in HCT116 cells, and the inhibition of autophagy strengthened the proapoptotic effect of PpIX-PDT. Thus, the appropriate modulation of autophagy may be as a potential therapeutic target for colon cancer cells treated with PpIX-PDT.
AB - Background: Photodynamic therapy (PDT) has been reported to be a promising therapy for colon cancer because of its substantial safety features and its ability to induce a systematic reaction rather than local effects on the focal lesion in the intestine. Autophagy and apoptosis play important roles in the response to PDT. However, the role of autophagy after PDT treatment has not yet been clarified. Methods: In this study, we investigated the relationship between apoptosis and autophagy in porphyrin IX (PpIX)-mediated PDT (PpIX-PDT) in HCT116 colon cancer cells. PpIX-PDT decreased cell viability in a concentration- and light dose-dependent manner. Results: PpIX-PDT results in nuclear condensation, increased the expression of Caspase-3, Bax, and PARP, and decreased expression of Bcl-2. PpIX-PDT also induces the double membrane autophagosome, up-regulates LC3B, Atg7, Beclin-1, and Bcl-2 expression and down-regulates P62 expression. Inhibition of autophagy using chloroquine (CQ) or Atg7 knockdown with a shRNA enhances apoptotic cell death. Based on these findings, autophagy plays a self-protective role in HCT116 cells in response to PpIX-PDT treatment. Discussion: Both autophagy and apoptosis were induced by PpIX-PDT in HCT116 cells, and the inhibition of autophagy strengthened the proapoptotic effect of PpIX-PDT. Thus, the appropriate modulation of autophagy may be as a potential therapeutic target for colon cancer cells treated with PpIX-PDT.
KW - Apoptosis
KW - Autophagy
KW - Colorectal cancer
KW - Photodynamic therapy
KW - Porphyrin IX
UR - http://www.scopus.com/inward/record.url?scp=85042273902&partnerID=8YFLogxK
U2 - 10.1016/j.pdpdt.2018.01.010
DO - 10.1016/j.pdpdt.2018.01.010
M3 - Article
C2 - 29355734
AN - SCOPUS:85042273902
SN - 1572-1000
VL - 21
SP - 396
EP - 403
JO - Photodiagnosis and Photodynamic Therapy
JF - Photodiagnosis and Photodynamic Therapy
ER -
