Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways

Wan He1, Zhijian Xu2, Dongliang Song1

  • 1Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Life Sciences
|January 12, 2020
PubMed
Abstract

Insights

Rafoxanide effectively treats diffuse large B-cell lymphoma (DLBCL) by inhibiting cell viability and inducing apoptosis. This novel therapy shows promise for DLBCL patients with poor prognoses, reducing tumor growth in preclinical models.

Area of Science:

  • Oncology
  • Hematology
  • Pharmacology

Background:

  • Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoid malignancy with limited treatment options.
  • Previous research demonstrated rafoxanide's efficacy in treating multiple myeloma (MM).

Purpose of the Study:

  • To evaluate the anti-cancer effects of rafoxanide on DLBCL.
  • To elucidate the molecular mechanisms underlying rafoxanide's action in DLBCL.

Main Methods:

  • Cell viability and apoptosis assessed via CCK-8 assay and flow cytometry.
  • Western blot used to analyze protein and pathway regulation.
  • Xenograft mouse models employed for in vivo efficacy studies, with TUNEL and immunofluorescence assays.

Main Results:

  • Rafoxanide significantly inhibited DLBCL cell viability and induced apoptosis.
  • The compound caused cell cycle arrest, reduced mitochondrial membrane potential, and increased reactive oxygen species (ROS).
  • Rafoxanide modulated PTEN/PI3K/AKT and JNK/c-Jun pathways, upregulated H2AX phosphorylation, and inhibited DNA repair, leading to reduced tumor volume in vivo.

Conclusions:

  • Rafoxanide demonstrates significant anti-DLBCL activity through multiple molecular mechanisms.
  • These findings suggest rafoxanide as a potential novel therapeutic agent for DLBCL.

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