Protein 4.1R affects photodynamic therapy for B16 melanoma by regulating the transport of 5-aminolevulinic acid

Journal Article · Mon Feb 15 04:00:00 EST 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2020.112465· OSTI ID:23195368

Li, Bowen ^[1]; Zhang, Xiaolin ^[2]; Lu, Yu ^[1]; Zhao, Luyang ^[3]; Guo, Yaxin ^[1]; others, and

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1. Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, Henan (China)
2. People's Hospital of Zhengzhou, 33 Huanghe Road, Zhengzhou, 450000, Henan (China)
3. BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan (China)

Highlights: • Protein 4.1R knockout promoted the proliferation, migration, and invasion of B16 cells. • Protein 4.1R knockout induced a decrease expression of 5-ALA transporters GAT-1 and GAT-2. • Protein 4.1R knockout reduced the effect of PDT and downregulated the anti-tumor immune response induced by PDT. Melanoma is the most aggressive malignant tumor of skin cancer as it can grow rapidly and metastasize. Photodynamic therapy (PDT) is a promising cancer ablation method for skin tumors, although it lacks efficiency owing to factors such as tumor characteristics, delivery of photosensitizers, immune response in vivo etc. Extensive investigation of molecules that can potentially modulate treatment efficacy is required. Protein 4.1R is a cytoskeletal protein molecule. Previous studies have shown that protein 4.1R knockdown reduces PDT sensitivity in mouse embryonic fibroblast cells. However, the functional role of protein 4.1R in melanoma is unclear. In this study, we aimed to elucidate the effect of protein 4.1R on PDT for melanoma in mice and the mechanism of anti-tumor immunity. Our results indicated that CRISPR/Cas9-mediated protein 4.1R knockout promotes the proliferation, migration, and invasion of B16 cells. We further investigated the potential mechanism of protein 4.1R on tumor cell PDT sensitivity. Our results showed that protein 4.1R knockout reduced the expression of membrane transporters γ-aminobutyric acid transporter (GAT)-1 and (GAT)-2 in B16 cells, which affected 5-ALA transmembrane transport and reduced the efficiency of PDT on B16 cells. Protein 4.1R knockout downregulated the anti-tumor immune response triggered by PDT in vivo. In conclusion, our data suggest that protein 4.1R is an important regulator in PDT for tumors and may promote the progress and efficacy of melanoma treatment.

• OSTI ID: 23195368
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 399; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINOBUTYRIC ACID
AMINOLEVULINIC ACID
CELL PROLIFERATION
FIBROBLASTS
IMMUNITY
IN VIVO
KNOCK-OUT REACTIONS
MELANOMAS
MEMBRANE TRANSPORT
MICE
PHOTODYNAMIC THERAPY
PROTEINS
SENSITIVITY
SKIN
TUMOR CELLS