Arsenic Trioxide inhibits Activation of Hedgehog Pathway in Human Neuroblastoma Cell Line SK-N-BE(2) Independent of Itraconazole

  • Autores: Liu X.1, Wang Z.2, Xiong X.3, Li C.4, Wu Y.3, Su M.3, Yang S.3, Zeng M.3, Weng W.3, Huang K.3, Zhou D.3, Fang J.3, Xu L.3, Li P.5, Zhu Y.6, Qiu K.3, Ma Y.7, Lei J.3, Li Y.3
  • Afiliações:
    1. Pediatric Hematology/Oncology, Children's Medical Center,, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    2. Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    3. Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    4. Department of Pediatrics, the Seventh Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University
    5. South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
    6. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital
    7. Pediatric Hematology/Oncology, Children's Medical Cente, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Edição: Volume 23, Nº 20 (2023)
  • Páginas: 2217-2224
  • Seção: Oncology
  • URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694391
  • DOI: https://doi.org/10.2174/0118715206259952230919173611
  • ID: 694391

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Resumo

Background: Neuroblastoma (NB) remains associated with a low overall survival rate over the long term. Abnormal activation of the Hedgehog (HH) signaling pathway can activate the transcription of various downstream target genes that promote NB. Both arsenic trioxide (ATO) and itraconazole (ITRA) can inhibit tumor growth.

Objective: To determine whether ATO combined with ITRA can be used to treat NB with HH pathway activation, we examined the effects of ATO and ITRA monotherapy or combined inhibition of the HH pathway in NB.

Methods: Analysis of CCK8 and flow cytometry showed cell inhibition and cell cycle, respectively. Real-time PCR analysis was conducted to assess the mRNA expression of HH pathway.

Results: We revealed that as concentrations of ATO and ITRA increased, the killing effects of both agents on SK-N-BE(2) cells became more apparent. During G2/M, the cell cycle was largely arrested by ATO alone and combined with ITRA, and in the G0/G1 phase by ITRA alone. In the HH pathway, ATO inhibited the transcription of the SHH, PTCH1, SMO and GLI2 genes, however, ITRA did not. Instead of showing synergistic effects in a combined mode, ITRA decreased ATO inhibitory effects.

Conclusion: We showed that ATO is an important inhibitor of HH pathway but ITRA can weaken the inhibitory effect of ATO. This study provides an experimental evidence for the clinical use of ATO and ITRA in the treatment of NB with HH pathway activation in cytology.

Sobre autores

Xiaoshan Liu

Pediatric Hematology/Oncology, Children's Medical Center,, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Zhixuan Wang

Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Xilin Xiong

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Chunmou Li

Department of Pediatrics, the Seventh Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University

Email: info@benthamscience.net

Yu Wu

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Mingwei Su

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Shu Yang

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Meilin Zeng

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Wenjun Weng

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Ke Huang

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Dunhua Zhou

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Jianpei Fang

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Lvhong Xu

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Peng Li

South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

Email: info@benthamscience.net

Yafeng Zhu

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital

Email: info@benthamscience.net

Kunyin Qiu

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Yuhan Ma

Pediatric Hematology/Oncology, Children's Medical Cente, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Jiaying Lei

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Email: info@benthamscience.net

Yang Li

Pediatric Hematology/Oncology, Children's Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Autor responsável pela correspondência
Email: info@benthamscience.net

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