Related Experiment Video
Updated: Jul 9, 2026
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using
Hiroaki Yamaguchi1, Minako Kobayashi, Masahiro Okada
1Department of Pharmaceutical Sciences, Tohoku University Hospital, Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Abstract:
A rapid screening system has been established to extract novel candidates that exhibit potent inhibition of the transport of fluorescent substrate by organic anion transporting polypeptide (OATP) 1B3. OATP1B3 is abundantly expressed in solid digestive organ cancers. Thus, the identification of new substrates leads to novel strategies for effective cancer chemotherapy with minimal adverse effects. We used an automated image acquisition and analysis system (IN Cell Analyzer 1000) to visualize the transport and subsequent accumulation of the fluorescent substrate chenodeoxycholyl-(Nepsilon-NBD)-lysine (CDCA-NBD). Antineoplastic screening demonstrated that five candidates agents, docetaxel, actinomycin D, mitoxantrone, paclitaxel, and SN-38, exhibited potent inhibitory effects on OATP1B3-mediated transport of CDCA-NBD. To clarify if these antineoplastic drugs are substrates for OATP1B3, we performed transport assays in OATP1B3-expressing cells. We determined that SN-38 is a novel substrate for OATP1B3. In conclusion, our results demonstrate that the screening system established in this study is a useful method for the rapid extraction of candidate therapeutic agents from the large numbers of compounds.
Insights
A new screening system identifies potential cancer drugs by measuring inhibition of organic anion transporting polypeptide (OATP) 1B3. SN-38 was confirmed as a novel OATP1B3 substrate, offering new chemotherapy strategies.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Organic anion transporting polypeptide (OATP) 1B3 is highly expressed in digestive organ cancers.
- Targeting OATP1B3 offers potential for novel cancer chemotherapy with reduced side effects.
- Identifying OATP1B3 substrates and inhibitors is crucial for developing effective cancer treatments.
Purpose of the Study:
- To establish a rapid screening system for identifying inhibitors of OATP1B3-mediated transport.
- To discover novel substrates and inhibitors of OATP1B3 for potential cancer therapy.
- To evaluate the inhibitory effects of antineoplastic agents on OATP1B3 activity.
Main Methods:
- Utilized an automated image analysis system (IN Cell Analyzer 1000) to monitor fluorescent substrate (CDCA-NBD) transport.
- Performed antineoplastic screening to identify compounds inhibiting OATP1B3.
- Conducted transport assays in OATP1B3-expressing cells to confirm drug substrates.
Main Results:
- A rapid screening system for OATP1B3 inhibitors was successfully established.
- Five antineoplastic agents (docetaxel, actinomycin D, mitoxantrone, paclitaxel, SN-38) showed potent inhibition of OATP1B3.
- SN-38 was identified as a novel substrate for OATP1B3.
Conclusions:
- The developed screening system is effective for rapidly identifying potential therapeutic agents.
- The findings provide a basis for novel cancer chemotherapy strategies targeting OATP1B3.
- SN-38's role as an OATP1B3 substrate opens new avenues for drug development in digestive organ cancers.
