2. Academic Validation
  3. HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU

HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU

  • Biosci Rep. 2021 Apr 30;41(4):BSR20203905. doi: 10.1042/BSR20203905.
Jun Sun  # 1 2,  Wei Wu  # 3,  Xiaofeng Tang  # 1,  Feifei Zhang 1,  Cheng Ju 1 4,  Renfeng Liu 1 4,  Yiping Liang 1 5,  Bo Yu 1 4,  Bin Lv 1 4,  Yuhong Guo 1 4,  Duo Zeng 1 4,  Xuchang Tao 6,  Min Wang 7,  Zhiping Zhang 4,  Changhua Zhang 2,  Xiao-Bin Lv 1
Affiliations

Affiliations

  • 1 Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Center Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang 330008, China.
  • 2 College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
  • 3 Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huangzhou, Hubei 438000, China.
  • 4 Nanchang Key Laboratory of Orthopedics, The Third Affiliated Hospital of Nanchang University, Nanchang 330008, China.
  • 5 College of Life Science, Jiangxi Agriculture University, Nanchang 330045, China.
  • 6 Department of Nuclear Medicine, The Third Affiliated Hospital of Nanchang University, Nanchang 330008, China.
  • 7 Department of Orthopedics, Tianjin General Hospital, Tianjin 300052, China.
  • # Contributed equally.
PMID: 33860796 DOI: 10.1042/BSR20203905
Abstract

Background: WT161, as a selective HDAC6 Inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms.

Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell Apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo.

Results: WT161 suppressed the cell growth and induced Apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (Akt). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo.

Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

Keywords

5-FU; PTEN; WT161; apoptosis; osteosarcoma; synergistic inhibition.

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