Open AccessInhibition of breast cancer cell growth by methyl pyropheophenylchlorin photodynamic therapy is mediated though endoplasmic reticulum stress‐induced autophagy in vitro and vivo
Author(s) -
Zhu Jiang,
Tian Si,
Li KaiTing,
Chen Qing,
Jiang Yuan,
Lin HaiDan,
Yu LeHua,
Bai DingQun
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1418
Subject(s) - autophagy , unfolded protein response , in vivo , endoplasmic reticulum , apoptosis , viability assay , photodynamic therapy , programmed cell death , cancer research , microbiology and biotechnology , western blot , cell growth , intracellular , chemistry , biology , biochemistry , organic chemistry , gene
Autophagy and ER stress participated in the inhibition of MPP a‐ PDT on tumor growth, but the molecular links between them remain undefined. We just explore the molecular mechanism between them in vitro and vivo. CCK ‐8 assay and flow cytometer were used to detect the cytotoxicity and mode of cell death after MPP a‐ PDT . Furthermore, the role of autophagy was verified in MPP a‐ PDT . Confocal microscopy was used to show the intracellular distribution of MPP a. ER stress markers and PERK signaling pathway were detected by western blot. While in vivo, tumor histology and immunohistochemistry were performed to show the effect of MPP a‐ PDT in mice. After MPP a‐ PDT , cells viability decreased in dose‐dependent manner. Besides, the cell apoptosis increased along with the increasing of Beclin‐1and LC 3B II but declining of P62. When pretreated with 3‐ MA , LC 3B II formation and the cytotoxicity declined. MPP a‐ PDT caused increasing of ER stress markers ( GRP 78, CHOP ) as MPP a accumulated in ER . However, pretreatment with ER stress inhibitor 4 PBA , the expression of GRP 78 and LC 3B II was blocked but the PERK signaling pathway activated and the expression of P62 increased. In vivo, the tumor growth was significantly inhibited by MPP a‐ PDT . Besides, the appearance of ER stress and autophagy was further demonstrated by immunohistochemistry. Our findings demonstrate that autophagy mediated by MPP a‐ PDT was regulated by ER stress, via PERK signaling pathway, to kill MDA ‐ MB ‐231 cells in vitro and vivo.