Delivery of Protein Kinase A by CRISPRMAX and Its Effects on Breast Cancer Stem-Like Properties.

CRISPRMAX cancer stem cells chemoresistance drug delivery epithelial-mesenchymal transition protein kinase A

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
23 Dec 2020
Historique:
received: 06 11 2020
revised: 14 12 2020
accepted: 18 12 2020
entrez: 30 12 2020
pubmed: 31 12 2020
medline: 31 12 2020
Statut: epublish

Résumé

Protein kinase A (PKA) activation has recently been reported to inhibit epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) ability, which is considered to be responsible for chemoresistance and tumor recurrence in patients. While current studies mainly focus on gene manipulation of the EMT process, the direct delivery of PKA enzymes to cancer cells has never been investigated. Here, we utilize the commercial Lipofectamine CRISPRMAX reagent to directly deliver PKAs to breast cancer cells and evaluate its effects on EMT regulation. We optimized the delivery parameters with fluorescent-labeled bovine serum albumin, and successfully delivered fluorescent PKAs through CRISPRMAX into breast cancer cells. Then, we evaluated the biological effects by immunofluorescence, flow cytometry, mammosphere assay, and chemoresistance assay. Our data showed the expression of EMT-related markers, α-smooth muscle actin and N-cadherin, was downregulated after CRISPRMAX-PKA treatment. Although the CD44

Identifiants

pubmed: 33374889
pii: pharmaceutics13010011
doi: 10.3390/pharmaceutics13010011
pmc: PMC7824330
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Distinguished Clinical Investigator Grant of Jiangsu Province, China
ID : JSTP201701
Organisme : Jiangsu Provincial Key Research and Development Programme
ID : BE2018690
Organisme : Academy of Finland
ID : 328933
Organisme : Sigrid Juséliuksen Säätiö
ID : 28002247K1
Organisme : China Scholarships Council
ID : No. 201803170073, No.201909110009

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Auteurs

Jun-Nian Zhou (JN)

Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China.
Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Turku Bioscience Center, University of Turku, 20520 Turku, Finland.
Turku Bioscience Center, Åbo Akademi University, 20520 Turku, Finland.

Tzu-Chen Rautio (TC)

Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Biomedical Imaging, Faculty of Medicine, University of Turku, 20520 Turku, Finland.

Chang Liu (C)

Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Turku Bioscience Center, University of Turku, 20520 Turku, Finland.
Turku Bioscience Center, Åbo Akademi University, 20520 Turku, Finland.

Xiao-Yu Xu (XY)

Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Turku Bioscience Center, University of Turku, 20520 Turku, Finland.
Turku Bioscience Center, Åbo Akademi University, 20520 Turku, Finland.

Dong-Qing Wang (DQ)

Department of Radiology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, China.

Yong Guo (Y)

Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Turku Bioscience Center, University of Turku, 20520 Turku, Finland.
Turku Bioscience Center, Åbo Akademi University, 20520 Turku, Finland.
Department of Endocrinology, Key Laboratory of National Health and Family Planning Commission for Male Reproductive Health, National Research Institute for Family Planning, Beijing 100081, China.

John Eriksson (J)

Turku Bioscience Center, University of Turku, 20520 Turku, Finland.
Turku Bioscience Center, Åbo Akademi University, 20520 Turku, Finland.

Hongbo Zhang (H)

Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Turku Bioscience Center, University of Turku, 20520 Turku, Finland.
Turku Bioscience Center, Åbo Akademi University, 20520 Turku, Finland.

Classifications MeSH