Effects of evodiamine on PI3K/Akt and MAPK/ERK signaling pathways in pancreatic cancer cells

Hong,Zhong; Wang,Zhaohong; Zhou,Bin; Wang,Jisheng; Tong,Hongfei; Liao,Yi; Zheng,Peng; Jamshed,Muhammad Babar; Zhang,Qiyu; Chen,Hui

doi:10.3892/ijo.2020.4956

Effects of evodiamine on PI3K/Akt and MAPK/ERK signaling pathways in pancreatic cancer cells

Authors:
- Zhong Hong
- Zhaohong Wang
- Bin Zhou
- Jisheng Wang
- Hongfei Tong
- Yi Liao
- Peng Zheng
- Muhammad Babar Jamshed
- Qiyu Zhang
- Hui Chen
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Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: January 10, 2020 https://doi.org/10.3892/ijo.2020.4956
Pages: 783-793
Copyright: © Hong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The effective antitumor drug evodiamine (EVO) is attracting increased attention. Therefore, the present study aimed to investigate the effects of EVO on the proliferation, apoptosis and autophagy of human pancreatic cancer (PC) cell lines in vitro and in vivo. Human PANC‑1 and SW1990 PC cell lines were treated with different concentrations of EVO and proliferation was detected using a Cell Counting Kit (CCK)‑8 assay. Colony formation and wound‑healing assays showed that EVO inhibited PC cell viability and migration, and apoptosis was detected using flow cytometry. Western blotting and immunofluorescence detected the expression of proteins in PANC‑1 and SW1990 cells. The PANC‑1 cells were used to establish an orthotopic pancreatic tumor model in nude mice. Tumor‑bearing nude mice were administered with different concentrations of EVO, and growth was monitored. High‑resolution positron emission tomography and fluorine‑18‑labeled fluorodeoxyglucose were used to monitor the tumor/non‑tumor (T/NT) ratio and standard uptake value (SUV) of the mice, which were subsequently sacrificed to measure the transplanted tumor weight. Apoptosis increased with increasing EVO concentration. The EVO‑treated PC cells exhibited significantly higher expression of LC3II than the controls cells. EVO decreased LC3II, enhanced P62 and inhibited the expression of Akt, extracellular‑signal‑regulated protein kinase (ERK)1/2 and p38. Compared with the control group, the T/NT ratio, SUV and tumor weight decreased more markedly in the EVO‑treated group. The tumor expression of phosphorylated AKT, detected using immunohistochemistry, decreased with increasing EVO doses in vivo. EVO induced PC cell apoptosis by inhibiting phosphoinositide 3‑kinase/AKT and mitogen‑activated protein kinase/ERK and inhibiting the phosphorylation of signal transducer and activator of transcription activator 3 in PC cells to inhibit autophagy, suggesting that EVO may be considered as a novel PC treatment.

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