Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by betulinic acid‑loaded nanoliposomes in colorectal cancer

Wang,Gang; Yu,Yang; Wang,Yu‑Zhu; Zhu,Zhi‑Min; Yin,Pei‑Hao; Xu,Ke

doi:10.3892/or.2020.7787

Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by betulinic acid‑loaded nanoliposomes in colorectal cancer

Authors:
- Gang Wang
- Yang Yu
- Yu‑Zhu Wang
- Zhi‑Min Zhu
- Pei‑Hao Yin
- Ke Xu
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Affiliations: Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, P.R. China, Jiangsu University School of Pharmacy, Zhenjiang, Jiangsu 212001, P.R. China, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
Published online on: October 1, 2020 https://doi.org/10.3892/or.2020.7787
Pages: 2595-2609
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA‑loaded nanoliposomes (BA‑NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA‑NLs in fatty acid metabolism‑mediated glycolysis, and investigate the role of key targets, such as acyl‑CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase‑1 (PFK‑1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA‑NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti‑CRC function of BA‑NLs. Moreover, the effects of BA‑NLs were further validated by demonstrating that the key targets of HK2, PFK‑1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA‑NLs, which play key roles in the inhibition of glycolysis and fatty acid‑mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.

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