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SLAMF1 Promotes Methotrexate Resistance via Activating Autophagy in Choriocarcinoma Cells

Dazun Shi1, Yu Zhang1, Yan Tian1

  • 1Department of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan Province, People's Republic of China.

Cancer Management and Research
|January 7, 2021
PubMed
Abstract

Insights

Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) promotes methotrexate resistance in choriocarcinoma by activating protective autophagy. Targeting SLAMF1 could sensitize choriocarcinoma cells to methotrexate treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Methotrexate (MTX) resistance is a significant hurdle in treating choriocarcinoma.
  • Understanding the molecular mechanisms of chemoresistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) in mediating MTX chemoresistance in choriocarcinoma.
  • To explore the potential of targeting SLAMF1 as a therapeutic strategy.

Main Methods:

  • Established MTX-resistant choriocarcinoma cell lines (JEG3/MTX, JAR/MTX).
  • Assessed cell viability, clonogenesis, and autophagy.
  • Analyzed SLAMF1 expression using Western blotting.
  • Utilized SLAMF1 knockdown and constitutive expression models.

Main Results:

  • SLAMF1 expression was upregulated in MTX-resistant cells.
  • SLAMF1 knockdown reduced cell viability and clonogenesis in MTX-treated resistant cells.
  • SLAMF1 expression promoted survival in MTX-treated sensitive cells.
  • Autophagy was activated in MTX-resistant cells, and SLAMF1 depletion suppressed autophagy and induced apoptosis.

Conclusions:

  • SLAMF1 contributes to MTX resistance in choriocarcinoma by activating protective autophagy.
  • Targeting SLAMF1 may enhance the efficacy of MTX-based chemotherapy for choriocarcinoma.
Keywords:
SLAMF1autophagychoriocarcinomadrug resistancemethotrexate

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