MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS
Authors: Dingqun Bai
Lehua Yu
Liyi Huang
Haidan Lin
Qing Chen
Journal: BMC Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: Breast tumor; Invasion; Migration; Photodynamic therapy; Reactive oxygen species.
Affiliations: Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China., Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China., Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China. .

Abstract:  Background: Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells. Methods: Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining. Results: Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced the expression of F-actin in cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion: Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis. 

Retracted: No

PubPeer comments:
 2021 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0247083 After this article [1] was published, further analysis revealed that the sample used for the reported genome analysis was more likely from the closely related species, Dolly Varden (Salvelinus malma), or may have been from a hybrid between the two species. We stand by the genome and transcriptome assembly as scientifically valid and representative of the sample analyzed. However, the identity of that individual is now in question and consequently the articleu2019s title, results, and conclusions attributing the sequences to Arctic charr are not upheld. In light of this issue, we retract the article. We have also requested that NCBI change the species name on the genome sequence deposition to indicate that the data were derived from unclassified species in the Salvelinus genus, or Salvelinus sp. The authors apologize for the issues with this article. AS and RM either could not be reached or did not respond to correspondence about this retraction. The other authors all agreed with the retraction decision. Reference 1. Christensen KA, Rondeau EB, Minkley DR, Leong JS, Nugent CM, Danzmann RG, et al. (2018) The Arctic charr (Salvelinus alpinus) genome and transcriptome assembly. PLoS ONE 13(9): e0204076. https: doi.org 10.1371 journal.pone.0204076 ,