2. Academic Validation
  3. Synergistic Effect of Statins and Abiraterone Acetate on the Growth Inhibition of Neuroblastoma via Targeting Androgen Receptor

Synergistic Effect of Statins and Abiraterone Acetate on the Growth Inhibition of Neuroblastoma via Targeting Androgen Receptor

  • Front Oncol. 2021 May 10;11:595285. doi: 10.3389/fonc.2021.595285.
Zengchun Hu 1 2,  Chuandong Cheng 3 4,  Yue Wang 1 5,  Tianrui Chen 6,  Junhong Tu 1 5,  Chaoshi Niu 3 4,  Rong Xing 1 5,  Yang Wang 1 5,  Yinghui Xu 7
Affiliations

Affiliations

  • 1 Dalian Medical University, Dalian, China.
  • 2 Department of Neurosurgery, 2nd Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 3 Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 4 Division of Life Sciences and Medicine, Department of Neurosurgery, 1st Affiliated Hospital of University of Science and Technology of China, Hefei, China.
  • 5 Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
  • 6 Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
  • 7 Department of Neurosurgery, 1st Affiliated Hospital of Dalian Medical University, Dalian, China.
PMID: 34041015 DOI: 10.3389/fonc.2021.595285
Abstract

Neuroblastoma is the most common extracranial neuroendocrine tumor in childhood. Although many studies have tried to find effective treatments, there are still numerous limitations in current clinical targeted therapy. So, it is important to find new therapeutic targets and strategies from a new perspective. Our previous study reported that the Androgen Receptor (AR) promotes the growth of neuroblastoma in vitro and in vivo. Based on documentary investigation, we postulated that the AR-SCAP-SREBPs-CYP17/HMGCR axis may regulate Cholesterol and androgens synthesis and form a positive enhancement loop promoting NB progression. Clinical samples and Oncomine database analysis proved the activation of AR-SCAP-SREBPs-CYP17/HMGCR axis in neuroblastoma. The combination of inhibitors of HMGCR (statins) and CYP17A1 (abiraterone acetate) showed synergistic effect that significantly inhibited the proliferation and migration with decreased expression of related genes detected in vitro and in vivo suggesting the dual-targeted therapy had the potential to inhibit the progression of neuroblastoma in spite of its MYCN status. This study provides new ideas for clinical treatment of neuroblastoma with efficacy and reduced toxicity.

Keywords

SREBP cleavage activating protein; abiraterone acetate; androgen receptor; neuroblastoma; statin; synergistic effect.

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