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Updated: Jul 28, 2025

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Selective Inhibition of L-type Amino Acid Transporter 1 Suppresses Cell Proliferation in Ovarian Clear Cell Carcinoma

Masaki Sekine1, Iemasa Koh2, Kosuke Nakamoto1

  • 1Department of Obstetrics and Gynecology, Faculty of Medicine Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Anticancer Research
|May 29, 2023
PubMed
Abstract

Insights

Selective inhibition of L-type amino acid transporter 1 (LAT1) with nanvuranlat effectively reduces ovarian clear cell carcinoma (OCCC) cell proliferation by impacting leucine uptake and the mTOR pathway, offering a promising new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Ovarian clear cell carcinoma (OCCC) presents a poor prognosis and resistance to chemotherapy.
  • Novel therapeutic strategies are urgently needed for OCCC treatment.
  • L-type amino acid transporter 1 (LAT1) plays a role in cancer growth.

Purpose of the Study:

  • To investigate the effect of selective LAT1 inhibition on OCCC cell proliferation.
  • To evaluate nanvuranlat (JPH203) as a LAT1 inhibitor in OCCC.

Main Methods:

  • Assessed nanvuranlat's inhibition of [3H] leucine uptake in OCCC cells (JHOC9).
  • Analyzed cell proliferation kinetics and mTOR pathway phosphorylation.
  • Correlated LAT1 expression with progression-free survival (PFS) in clinical OCCC specimens.

Main Results:

  • Nanvuranlat dose-dependently inhibited [3H] leucine uptake and OCCC cell proliferation.
  • Nanvuranlat suppressed mTOR signaling pathway activity.
  • LAT1 expression was frequent in OCCC and correlated with PFS.

Conclusions:

  • Selective LAT1 inhibition suppresses OCCC cell proliferation by inhibiting leucine uptake and impacting the mTOR pathway.
  • LAT1 selective inhibition demonstrates potential as a therapeutic strategy for OCCC.
Keywords:
L-type amino acid transporter 1cell proliferationleucinemammalian target of rapamycinnanvuranlatovarian clear cell carcinoma

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