氯贝丁酯在淋巴瘤和多发性骨髓瘤的体外治疗中显示出疗效。

Clofibrate Demonstrates Efficacy in In Vitro Treatment of Lymphoma and Multiple Myeloma.

作者信息

Schmeel Leonard Christopher, Schmeel Frederic Carsten, Schmidt-Wolf Ingo G H

机构信息

Department of Radiology and Radiation Oncology, University Hospital Bonn, Bonn, Germany Center for Integrated Oncology (CIO), Medical Clinic and Polyclinic III, University Hospital Bonn, Bonn, Germany.

Center for Integrated Oncology (CIO), Medical Clinic and Polyclinic III, University Hospital Bonn, Bonn, Germany

出版信息

Anticancer Res. 2016 Jul;36(7):3395-400.

PMID:27354598

Abstract

BACKGROUND/AIM: Multiple myeloma (MM), a hematological malignancy of monoclonal B-lymphocytes, remains largely incurable and novel treatments are urgently required. Aberrant activation of wingless-related integration site (WNT)/β-catenin signaling has been demonstrated in both lymphoma and MM, rendering its signaling molecules attractive for the development of new targeted-therapies. Clofibrate has proven anticarcinogenic effects attributed to peroxisome proliferator-activated receptor alpha (PPARα) agonism, also affecting WNT-associated signaling molecules.

MATERIALS AND METHODS

The antitumor apoptotic effect of clofibrate at doses ranging from 0.1-600 μM was investigated on four human and one murine myeloma cell lines, as well as in two human lymphoma cell lines, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay.

RESULTS

Clofibrate significantly reduced cell viability in all tested myeloma and lymphoma cell lines in a dose-dependent manner, while healthy cells were hardly affected.

CONCLUSION

Given the known safety profile and induction of apoptosis at low effective doses, our data warrant further investigation of clofibrate as a novel therapy agent in MM.

摘要

背景/目的：多发性骨髓瘤（MM）是一种单克隆B淋巴细胞的血液系统恶性肿瘤，目前仍难以治愈，迫切需要新的治疗方法。在淋巴瘤和MM中均已证实无翅相关整合位点（WNT）/β-连环蛋白信号通路异常激活，这使得其信号分子成为开发新型靶向治疗药物的有吸引力的靶点。氯贝丁酯已被证明具有抗癌作用，归因于过氧化物酶体增殖物激活受体α（PPARα）激动作用，同时也影响WNT相关信号分子。