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Cancer Med. 2018 May;7(5):1908-1920. doi: 10.1002/cam4.1418. Epub 2018 Mar 25.

Inhibition of breast cancer cell growth by methyl pyropheophenylchlorin photodynamic therapy is mediated though endoplasmic reticulum stress-induced autophagy in vitro and vivo.

Author information

1
Department of Rehabilitation, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
2
Department of Rehabilitation, Southwest University Hospital, Chongqing, China.
3
Department of Rehabilitation, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Autophagy and ER stress participated in the inhibition of MPPa-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 MPPa-PDT. Furthermore, the role of autophagy was verified in MPPa-PDT. Confocal microscopy was used to show the intracellular distribution of MPPa. 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 MPPa-PDT in mice. After MPPa-PDT, cells viability decreased in dose-dependent manner. Besides, the cell apoptosis increased along with the increasing of Beclin-1and LC3B II but declining of P62. When pretreated with 3-MA, LC3B II formation and the cytotoxicity declined. MPPa-PDT caused increasing of ER stress markers (GRP78, CHOP) as MPPa accumulated in ER. However, pretreatment with ER stress inhibitor 4PBA, the expression of GRP78 and LC3B II was blocked but the PERK signaling pathway activated and the expression of P62 increased. In vivo, the tumor growth was significantly inhibited by MPPa-PDT. Besides, the appearance of ER stress and autophagy was further demonstrated by immunohistochemistry. Our findings demonstrate that autophagy mediated by MPPa-PDT was regulated by ER stress, via PERK signaling pathway, to kill MDA-MB-231 cells in vitro and vivo.

KEYWORDS:

Autophagy; endoplasmic reticulum stress; methyl pyropheophenylchlorin; photodynamic therapy

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