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Autophagy in drug resistance of the multiple myeloma cell line RPMI8226 to doxorubicin

Y-Z Pan1, X Wang1, H Bai1

  • 1Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.

Genetics and Molecular Research : GMR
|July 1, 2015
PubMed

Insights

Autophagy activation in multiple myeloma (MM) cells contributes to doxorubicin (DOX) resistance. Inhibiting autophagy partially reversed drug resistance, suggesting it

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Multiple myeloma (MM) is a hematologic malignancy.
  • Drug resistance is a major challenge in MM treatment.
  • Autophagy plays a role in cellular stress response and drug resistance.

Purpose of the Study:

  • To investigate the role of autophagy in doxorubicin (DOX) resistance in multiple myeloma (MM).

Main Methods:

  • Developed a DOX-resistant MM cell line (RPMI8226/DOX).
  • Assessed drug resistance using MTT assay.
  • Detected autophagy via transmission electron microscopy, immunofluorescence, and Western blotting.
  • Analyzed apoptosis changes using flow cytometry after autophagy inhibition.

Main Results:

  • RPMI8226/DOX cells exhibited a drug resistance index of 10.8.
  • Autophagy and lysosomal activity were observed in DOX-resistant cells.
  • Increased light chain 3-II protein expression confirmed higher autophagy in resistant cells.
  • Inhibiting autophagy with hydroxychloroquine or 3-methyladenine partially reversed DOX resistance.

Conclusions:

  • Autophagy activation is linked to doxorubicin resistance in multiple myeloma.
  • Targeting autophagy may be a potential strategy to overcome drug resistance in MM.

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