The dual HDAC and PI3K inhibitor, CUDC‑907, inhibits tumor growth and stem‑like properties by suppressing PTX3 in neuroblastoma

Li,Mengzhen; Li,Mengzhen; Hu,Yang; Hu,Yang; Wang,Juan; Wang,Juan; Xu,Yanjie; Xu,Yanjie; Hong,Ye; Hong,Ye; Zhang,Li; Zhang,Li; Luo,Qiuyun; Luo,Qiuyun; Zhen,Zijun; Zhen,Zijun; Lu,Suying; Lu,Suying; Huang,Junting; Huang,Junting; Zhu,Jia; Zhu,Jia; Zhang,Yizhuo; Zhang,Yizhuo; Que,Yi; Que,Yi; Sun,Feifei; Sun,Feifei

doi:10.3892/ijo.2023.5602

The dual HDAC and PI3K inhibitor, CUDC‑907, inhibits tumor growth and stem‑like properties by suppressing PTX3 in neuroblastoma

Authors:
- Mengzhen Li
- Yang Hu
- Juan Wang
- Yanjie Xu
- Ye Hong
- Li Zhang
- Qiuyun Luo
- Zijun Zhen
- Suying Lu
- Junting Huang
- Jia Zhu
- Yizhuo Zhang
- Yi Que
- Feifei Sun
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Affiliations: Department of Pediatric Oncology, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
Published online on: December 8, 2023 https://doi.org/10.3892/ijo.2023.5602
Article Number: 14
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuroblastoma (NB) is one of the common solid tumors in childhood and poses a threat to the lives of children. Patients with advanced‑stage or recurrent NB have a poor prognosis. CUDC‑907, as a novel dual‑target inhibitor of histone deacetylase (HDAC) and phosphatidylinositol‑3‑kinase (PI3K), has been proven to play an antitumor role in several types of tumors. However, the exact role of CUDC‑907 in NB remains unclear. In the present study, in vivo and in vitro assays were performed to investigate the anti‑NB activity of CUDC‑907. Pentraxin 3 (PTX3) small interfering RNA (siRNA) and PTX3 overexpression plasmid were transfected into cells to define the underlying mechanisms of CUDC‑907. Tumor tissues and clinical information were collected and immunohistochemistry (IHC) was conducted to analyze the association between the expression of HDAC1, HDAC2, HDAC3 and CD44, and the prognosis of patients with NB. The results indicated that CUDC‑907 significantly inhibited the proliferation and migration, and induced the apoptosis of NB cells, downregulating the expression level of MYCN, and suppressing the PI3K/AKT and MAPK/ERK pathways. Furthermore, CUDC‑907 suppressed the stem‑like properties of NB cells by inhibiting PTX3, a ligand and upstream protein of CD44. IHC revealed that the high expression of HDAC1, 2, 3 and CD44 was associated with a poor prognosis of patients with NB. On the whole, these findings indicate that CUDC‑907 may be developed into a possible therapeutic approach for patients with NB.

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