和厚朴酚通过Raf/MEK/ERK通路调控糖酵解抑制胰腺癌细胞恶性进展

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中图分类号：R737.33 文献标志码：A DOI：10.7652/jdyxb202505015

Honokiol inhibits the malignant progression of pancreatic cancer cells by regulating glycolysis through the Raf/MEK/ERK pathway

LIU Xin1 ，LI Jing¹，WANG Xi²，DONG Lei³ （1. Department of Gastrointestinal Endoscopy Center，Shaanxi Provincial People’s Hospital， Xi'an 71Oo68；2. Department of Oncology，Shaanxi Provincial People's Hospital， Xi'an 7loo68；3. Department of Gastroenterology，The Second Affiliated Hospital of Xi'an Jiaotong University，Xi'an 7l0o04，China）

ABSTRACT：ObjectiveTo explore the effects of honokiol on malignant phenotypes in PANC-1 cels and its mechanisms.MethodsIn our experiments，MTT assay was used to detect the effects of honokiol on PANC-1 cel viability. The migration and invasion of PANC-1 cels were evaluated by wound healing assay and Transwellassy. The glycolysis level was detected by ELISA and ECAR.Western bloting was used to detect the expresions of OCT4，SOX2， Nanog，LDHA，HK2 and Raf/MEK/ERK pathway related proteins. ResultsHonokiol could significantly inhibit the migration and invasion abilities of PANC-1cells（migration rate and invasionrate being 13.78%-59.45% and 12.47%-44.47% ，respectively）. Mechanistically，honokiol targeted Raf/MEK/ERK signaling pathway and significantly reduced the expressions of LDHA （29.60%） ）and HK2（ 31.98%） ，thereby reducing glycolysis and lactate production （29.42%-56.31% ，compared with control group P<0.05; .This metabolic reprogramming effect ultimately inhibited the protein expressions of OCT4 33.38% ），SOX2 （33.07%） ： and Nanog （26.24%） .ConclusionHonokiol treatment can inhibit the cell viability，migration and invasion abilities ofPANC-1cells.The mechanisms are related to the inhibitionof glycolysisandcellstemnessbyregulating Raf/MEK/ERK pathway.

EY WORDS：honokiol；pancreatic cancer；cell stemness；glycolysis；ERK

胰腺癌是一种非常致命的肿瘤，一旦确诊多为中晚期，治疗选择非常有限并易对标准治疗形成耐药性，这些都使胰腺癌成为预后和生存率最差的肿瘤类型之一[]。（剩余10034字）