Journal
PHARMACOLOGICAL RESEARCH
Volume 165, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2020.105411
Keywords
Adenocarcinoma of the esophagogastric junction; Huaier; MEK/ERK signaling pathway; p-MEK; Invasion and metastasis
Categories
Funding
- Zhejiang Provincial Natural Science Foundation of China [LY18H290006, LR21H280001]
- National Natural Science Foundation of China [81903842, 81973634, 82074245]
- Program of Zhejiang Provincial TCM Sci-tech Plan [2018ZY006, 2020ZZ005, 2019ZZ010]
- Post-doctoral project of Zhejiang Province [ZJ2020128]
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This study demonstrated that high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG, and the traditional Chinese medicine Huaier exerts its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway both in vitro and in vivo.
The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.
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