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[The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma]

Meng-Ya Shi1, Yao Yao1, Ju Deng1

  • 1Institute of Hematology, Xuzhou Medical University; Department of Hematology, Xuzhou Medical University Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.

Zhongguo Shi Yan Xue Ye Xue Za Zhi
|June 9, 2021
PubMed
Abstract

Insights

The autophagy inhibitor ROC-325 significantly reduced multiple myeloma cell proliferation and induced apoptosis. Combination therapy with bortezomib overcame drug resistance, offering a potential new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma remains a significant challenge in hematologic malignancies.
  • Developing novel therapeutic strategies to overcome drug resistance is crucial.

Purpose of the Study:

  • To evaluate the effects of the autophagy inhibitor ROC-325, alone and in combination with bortezomib, on multiple myeloma cell lines.
  • To investigate the impact on cell proliferation, apoptosis, and autophagy.

Main Methods:

  • Multiple myeloma cell lines were treated with ROC-325.
  • Proliferation assessed by CCK-8 assay.
  • Apoptosis evaluated via Caspase-3/7 and Caspase-9 activity assays.
  • Autophagy detected by monodansylcadaverine staining and Western blot analysis of key proteins (PARP, Caspase-3, P62, Beclin-1, LC3A/B).
  • Synergistic effects with bortezomib on resistant cells were determined.

Main Results:

  • ROC-325 demonstrated dose-dependent inhibition of proliferation across multiple myeloma cell lines.
  • Increased Caspase activity and autophagic vacuole formation were observed with ROC-325 treatment.
  • Western blot analysis revealed altered expression of apoptosis and autophagy-related proteins.
  • Combined ROC-325 and bortezomib showed synergistic effects in inhibiting drug-resistant cells.

Conclusions:

  • ROC-325 inhibits myeloma cell proliferation and induces apoptosis via the mitochondrial pathway.
  • It also inhibits myeloma cell autophagy by interfering with autophagosome-lysosome fusion.
  • Combination therapy with ROC-325 and bortezomib can overcome bortezomib resistance in multiple myeloma.

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