Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells

Chen,Zi-Yi; Li,Jie; Zhu,Shu-Di; Li,Zhi-Di; Yu,Jia-Lin; Wu,Jie; Zhang,Chong; Zeng,Ling-Hui

doi:10.3892/etm.2022.11132

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells

Authors:
- Zi-Yi Chen
- Jie Li
- Shu-Di Zhu
- Zhi-Di Li
- Jia-Lin Yu
- Jie Wu
- Chong Zhang
- Ling-Hui Zeng
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Affiliations: School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, P.R. China, School of Pharmaceutical and Materials Engineering and Institute for Advanced Studies, Taizhou University, Taizhou, Zhejiang 318000, P.R. China
Published online on: January 7, 2022 https://doi.org/10.3892/etm.2022.11132
Article Number: 209
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The overall outcomes for patients with advanced liver cancer are far from satisfactory, and the development of more effective therapeutic strategies for liver cancer is required. Sulforhodamine blue and colony formation assays were performed to detect the proliferation of liver certain cancer cells, including HepG2 and Hep3B. Western blotting was also preformed to detect the expression of indicated proteins, including cleaved‑caspase‑3, cleaved‑poly (ADP‑ribose) polymerase, dual‑specificity tyrosine phosphorylation kinase 1A (DYRK1A), PARP‑1/2, GAPDH, myeloid cell leukemia‑1, phosphorylated‑AKT (Ser473), caspase‑3, α‑tubulin and AKT. PI staining was used to detect cell death. In the present study, DYRK1A knockdown significantly enhanced the anti‑liver cancer effect of regorafenib in vitro. Furthermore, DYRK1A inhibitor harmine together with regorafenib provided synergistic anti‑liver cancer activity by suppressing cell proliferation. In addition, harmine significantly enhanced regorafenib‑induced cell death in liver cancer cells. It has been reported that AKT signaling is activated in regorafenib‑resistant cancer cells and plays a crucial role in the regulation of cellular sensitivity to regorafenib. In the present study, AKT was activated in regorafenib‑treated cells, and harmine could suppress the activation of AKT and reinforce the anti‑cancer effects of regorafenib via regulating AKT in liver cancer cells. These data indicated that harmine enhanced the anti‑cancer effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells via regulating the activation of AKT, and harmine plus regorafenib may be a potential therapeutic regimen for treating patients with liver cancer.

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