Role of Sodium Taurocholate Cotransporting Polypeptide as a New Reporter and Drug-Screening Platform: Implications for Preventing Hepatitis B Virus Infections
Journal
Molecular Imaging and Biology
Journal Volume
22
Journal Issue
2
Pages
313-323
Date Issued
2020
Author(s)
Abstract
Purpose: Sodium taurocholate cotransporting polypeptide (NTCP) is a transmembrane protein responsible for delivering indocyanine green (ICG), an ideal infrared fluorescent dye, from extracellular space into the cytoplasm. Additionally, NTCP located in the hepatocyte membrane is the portal for hepatitis B and D virus (HBV/HDV) infections. This study verified the feasibility of NTCP as a reporter and further established a drug-screening platform for HBV/HDV infections. Procedures: NTCP was transduced into HT-29, a colorectal cancer cell line. To examine the use of NTCP as a reporter, NTCP-expressing cells were treated with ICG and examined through flow cytometry, an in vivo imaging system (IVIS), and confocal microscopy. Furthermore, ICG was administrated to NTCP-expressing tumor-bearing nude mice and examined using the IVIS. To study the drug-screening platform, NTCP-expressing cells were treated with cyclosporin A, an NTCP inhibitor, and ICG, and examined using a multimode detection platform. Moreover, nude mice were injected with NTCP inhibitors and ICG, and subsequently, their ICG signal was examined in vivo and in the blood. Results: In the reporter study, the ICG signal was higher in NTCP-expressing cells/tumors than in control cells/tumors after ICG treatment. In the drug-screening platform study, NTCP-expressing cells had decreased ICG intensity after treatment with NTCP inhibitors and ICG. Nude mice that were administered cyclosporin A had lower ICG intensity in the liver and higher intensity in the peripheral tissue and blood. Conclusions: NTCP and ICG form an ideal reporter system with extensive applications in cancer biology, robust drug–drug interactions, and drug screening in HBV/HDV infections. ? 2019, World Molecular Imaging Society.
Subjects
cyclosporine; indocyanine green; sodium bile acid cotransporter; cotransporter; fluorescent dye; organic anion transporter; sodium-bile acid cotransporter; taurocholic acid; animal experiment; animal model; animal tissue; Article; confocal microscopy; controlled study; drug screening; ex vivo study; feasibility study; female; flow cytometry; hepatitis B; HT-29 cell line; in vivo study; mouse; nonhuman; priority journal; animal; Bagg albino mouse; chemistry; cytoplasm; delta agent hepatitis; genetics; HEK293 cell line; hepatitis B; Hepatitis B virus; Hepatitis delta virus; human; liver; liver cell; metabolism; nude mouse; reporter gene; tumor cell line; Animals; Cell Line, Tumor; Cyclosporine; Cytoplasm; Female; Fluorescent Dyes; Genes, Reporter; HEK293 Cells; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Hepatocytes; Humans; Indocyanine Green; Liver; Mice; Mice, Inbred BALB C; Mice, Nude; Organic Anion Transporters, Sodium-Dependent; Symporters; Taurocholic Acid
SDGs
Other Subjects
cyclosporine; indocyanine green; sodium bile acid cotransporter; cotransporter; fluorescent dye; organic anion transporter; sodium-bile acid cotransporter; taurocholic acid; animal experiment; animal model; animal tissue; Article; confocal microscopy; controlled study; drug screening; ex vivo study; feasibility study; female; flow cytometry; hepatitis B; HT-29 cell line; in vivo study; mouse; nonhuman; priority journal; animal; Bagg albino mouse; chemistry; cytoplasm; delta agent hepatitis; genetics; HEK293 cell line; hepatitis B; Hepatitis B virus; Hepatitis delta virus; human; liver; liver cell; metabolism; nude mouse; reporter gene; tumor cell line; Animals; Cell Line, Tumor; Cyclosporine; Cytoplasm; Female; Fluorescent Dyes; Genes, Reporter; HEK293 Cells; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Hepatocytes; Humans; Indocyanine Green; Liver; Mice; Mice, Inbred BALB C; Mice, Nude; Organic Anion Transporters, Sodium-Dependent; Symporters; Taurocholic Acid
Type
journal article