PFK15, a PFKFB3 antagonist, inhibits autophagy and proliferation in rhabdomyosarcoma cells

Wang,Chunhui; Qu,Jianghong; Yan,Siyuan; Gao,Quan; Hao,Sibin; Zhou,Dongsheng

doi:10.3892/ijmm.2018.3599

PFK15, a PFKFB3 antagonist, inhibits autophagy and proliferation in rhabdomyosarcoma cells

Authors:
- Chunhui Wang
- Jianghong Qu
- Siyuan Yan
- Quan Gao
- Sibin Hao
- Dongsheng Zhou
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Affiliations: Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Gynecology, Zhangqiu People's Hospital, Jinan, Shandong 250200, P.R. China, State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China, Department of Orthopedics, Zhangqiu People's Hospital, Jinan, Shandong 250200, P.R. China
Published online on: March 29, 2018 https://doi.org/10.3892/ijmm.2018.3599
Pages: 359-367
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Due to the high-level of metastatic and relapsed rates, rhabdomyosarcoma (RD) patients have a poor prognosis, and novel treatment strategies are required. Thereby, the present study evaluated the efficacy of PFK15, a PFKFB3 inhibitor, in RD cells to explore its potential underlying mechanism on the regulation of autophagy and proliferation in these cells. The effects of PFK15 on cell viability loss and cell death in different treatment groups, were evaluated by MTS assay, colony growth assay and immunoblotting, respectively. In addition, the autophagy levels were detected by electron microscopy, fluorescence microscopy and immunoblotting following PFK15 treatment, and the autophagic flux was analyzed with the addition of chloroquine diphosphate salt or by monitoring the level of p62. PFK15 was observed to evidently decrease the viability of RD cells, inhibit the colony growth and cause abnormal nuclear morphology. Furthermore, PFK15 inhibited the autophagic flux and cell proliferation, as well as induced apoptotic cell death in RD cells through downregulation of the adenosine monophosphate‑activated protein kinase (AMPK) signaling pathway. An AMPK agonist rescued the inhibited cell proliferation and autophagy induced by PFK15. In conclusion, PFK15 inhibits autophagy and cell proliferation via downregulating the AMPK signaling pathway in RD cells.

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