Resibufogenin inhibits the malignant characteristics of multiple myeloma cells by blocking the PI3K/Akt signaling pathway

Zhou,Yan; Hong,Zirui; Jin,Keting; Lin,Chenjun; Xiang,Jingjing; Ge,Hangping; Zheng,Zhiyin; Shen,Jianping; Deng,Shu

doi:10.3892/etm.2022.11368

Resibufogenin inhibits the malignant characteristics of multiple myeloma cells by blocking the PI3K/Akt signaling pathway

Authors:
- Yan Zhou
- Zirui Hong
- Keting Jin
- Chenjun Lin
- Jingjing Xiang
- Hangping Ge
- Zhiyin Zheng
- Jianping Shen
- Shu Deng
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Affiliations: Department of Hematology, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China, The First Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, The First Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
Published online on: May 13, 2022 https://doi.org/10.3892/etm.2022.11368
Article Number: 441
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Resibufogenin (RBG) is an active ingredient of toad venom that also has antitumor potential. The present study aimed to investigate the role of RBG in multiple myeloma (MM) and the underlying action mechanism involving the PI3K/Akt signaling pathway. A human MM cell line, RPMI8226, was treated with RBG and/or insulin‑like growth factor 1 (IGF‑1; an activator of the PI3K/AKT signaling pathway). Cell viability and apoptosis were detected using Cell Counting Kit‑8 and flow cytometry, respectively. Cell migration and invasion were detected using a Transwell assay. In addition, the epithelial‑mesenchymal transition (EMT)‑associated proteins (E‑cadherin, N‑cadherin and Vimentin) and the PI3K/AKT pathway‑associated proteins [AKT, phosphorylated (p)‑AKT, PI3K and p‑PI3K] were measured using western blotting. RBG inhibited the viability, migration and invasion, and promoted the apoptosis of RPMI8226 cells in a dose‑dependent manner. RBG at concentrations of 4 and 8 µM upregulated E‑cadherin, and downregulated N‑cadherin and Vimentin in RPMI8226 cells. RBG also decreased the protein expression of p‑AKT and p‑PI3K in a dose‑dependent manner. In addition, the intervention of IGF‑1 weakened the inhibitory effects of RBG on the malignant characteristics of MM cells. RBG‑induced inhibition of EMT and the PI3K/AKT pathway were also weakened by IGF‑1 treatment. In conclusion, RBG inhibited viability, migration, invasion and EMT, and promoted the apoptosis of MM cells by blocking the PI3K/AKT signaling pathway.

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