Cholesterol biosynthesis inhibitor RO 48‑8071 inhibits pancreatic ductal adenocarcinoma cell viability by deactivating the JNK and ERK/MAPK signaling pathway

Ding,Zhen; Gu,Yanan; Huang,Dake; Zhou,Hong; Zhu,Tingting; Luo,Xin; Zhang,Sumei; Zhang,Shengquan; Qian,Yeben

doi:10.3892/mmr.2021.12468

Cholesterol biosynthesis inhibitor RO 48‑8071 inhibits pancreatic ductal adenocarcinoma cell viability by deactivating the JNK and ERK/MAPK signaling pathway

Authors:
- Zhen Ding
- Yanan Gu
- Dake Huang
- Hong Zhou
- Tingting Zhu
- Xin Luo
- Sumei Zhang
- Shengquan Zhang
- Yeben Qian
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Comprehensive Laboratory, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: September 28, 2021 https://doi.org/10.3892/mmr.2021.12468
Article Number: 828
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The morbidity and mortality of pancreatic cancer have been continuously increasing, causing seven deaths per 100,000 individuals/year. At present, effective therapies are severely lacking, thus, highlighting the importance of developing novel therapeutic approaches. The present study aimed to investigate the inhibitory roles of the 2,3‑oxidosqualene cyclase inhibitor, RO 48‑8071 (RO), on pancreatic ductal adenocarcinoma. RO was used to treat the pancreatic cancer cell line (PANC‑1) in vitro to examine the effects of RO on cell viability, as well as to determine its potential molecular mechanism. Moreover, experiments in a xenograft model of subcutaneous tumors generated by injecting PANC‑1 cells hypodermically into nude mice were performed to observe the inhibition of RO on tumor growth. It was found that RO inhibited PANC‑1 cell viability when treatment was given for 24, 48 and 72 h. The in vivo study demonstrated that RO markedly inhibited subcutaneous tumor growth in nude mice. Further studies revealed that RO could induce cell cycle arrest in the G1 phase by regulating p27, cyclin B1 and cyclin E expression to inhibit PANC‑1 cell viability. Moreover, RO inactivated the JNK and ERK MAPK signaling pathway by decreasing the phosphorylation levels of JNK and ERK. Collectively, the present study demonstrated that RO served anti‑pancreatic cancer roles in vitro and in vivo, which may provide new ideas and facilitate the development of novel treatment options for pancreatic cancer.

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