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The Effect of Ras Homolog C/Rho-Associated Coiled-Protein Kinase (Rho/ROCK) Signaling Pathways on Proliferation and

Xianqi Feng1, Ling Zhang2, Shumin Nie3

  • 1Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
|October 11, 2019
PubMed

Insights

This study shows that inhibiting Rho/ROCK signaling pathways significantly reduces multiple myeloma cell growth and increases apoptosis. Treatments with epigenetic modifiers 5-aza-2-deoxycytidine and trichostatin A also decrease RhoC, ROCK1, and ROCK2 expression in these cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Multiple myeloma is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
  • The Ras homolog C/Rho-associated coiled-protein kinase (Rho/ROCK) signaling pathway plays a crucial role in cell proliferation, migration, and survival.
  • Dysregulation of Rho/ROCK signaling is implicated in the progression of various cancers, including multiple myeloma.

Purpose of the Study:

  • To investigate the impact of Rho/ROCK signaling pathway intervention on the biological characteristics of human multiple myeloma cell lines RPMI-8226 and U266.
  • To examine the expression levels of RhoC, ROCK1, and ROCK2 in these cell lines following various treatments.

Main Methods:

  • Human multiple myeloma cell lines (RPMI-8226 and U266) were treated with epigenetic modifiers (5-aza-2-deoxycytidine, trichostatin A) and Rho/ROCK pathway inhibitors (CCG-1423, NSC23766, fasudil).
  • Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8) assay and clone formation assays.
  • Apoptosis was evaluated by flow cytometry and TUNEL assay.
  • Gene and protein expression of RhoC, ROCK1, and ROCK2 were determined by qRT-PCR and Western blot.

Main Results:

  • Rho/ROCK inhibitors (CCG-1423, NSC23766, fasudil) significantly inhibited proliferation and induced apoptosis in RPMI-8226 and U266 cells in a dose- and time-dependent manner.
  • Treatment with 5-aza-2-deoxycytidine and trichostatin A decreased mRNA and protein expression of RhoC, ROCK1, and ROCK2, with combined treatment showing enhanced effects.
  • Inhibitors significantly increased apoptosis rates in both cell lines compared to the control group.

Conclusions:

  • Epigenetic modifiers 5-aza-2-deoxycytidine and trichostatin A effectively reduce RhoC, ROCK1, and ROCK2 expression in multiple myeloma cells.
  • Intervention targeting the Rho/ROCK signaling pathway significantly inhibits cell growth and induces apoptosis in human multiple myeloma cell lines.
  • These findings suggest that targeting Rho/ROCK signaling and epigenetic modifications could be a potential therapeutic strategy for multiple myeloma.

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