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Drug library screening identifies colchicine and shikonin as therapeutic candidates for methotrexate-resistant

Yuki Nishiko1, Kosuke Yoshida2, Akira Yokoi2

  • 1Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Biochemical and Biophysical Research Communications
|July 20, 2026
PubMed

Insights

Researchers screened over 1000 compounds to find new treatments for methotrexate-resistant choriocarcinoma. Colchicine and shikonin showed promise, with shikonin demonstrating significant antitumor activity in vivo, offering hope for improved therapies.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Choriocarcinoma, a rare gestational trophoblastic neoplasia, presents a significant therapeutic challenge due to methotrexate resistance.
  • Methotrexate resistance is a critical clinical obstacle in treating choriocarcinoma.

Purpose of the Study:

  • To identify novel therapeutic compounds effective against methotrexate-resistant choriocarcinoma.
  • To screen a diverse drug library for potential choriocarcinoma treatments.

Main Methods:

  • Established methotrexate-resistant JAR and JEG-3 cell lines via stepwise drug exposure.
  • Conducted a two-step in vitro drug screening of over 1000 compounds.
  • Performed in vivo experiments to evaluate the efficacy of promising compounds.

Main Results:

  • Identified 55 compounds reducing cell viability by over 75% in resistant cell lines.
  • Colchicine and shikonin exhibited significant cytotoxicity against methotrexate-resistant choriocarcinoma cells.
  • Shikonin demonstrated notable in vivo antitumor activity, while colchicine showed limited efficacy.

Conclusions:

  • Colchicine and shikonin possess antitumor activity against methotrexate-resistant choriocarcinoma.
  • These compounds represent potential therapeutic candidates warranting further investigation.
  • Novel drug screening identified promising agents for challenging choriocarcinoma cases.
Keywords:
ChoriocarcinomaColchicineDrug library screeningMethotrexate resistanceShikonin

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