Effect Of 6-shogaol In Human Endometrial Carcinoma Ishikawa And Its Mechanism

Ginger is the rhizome of Zingiber officinale Roscoe,as one of the most commonly used spices and flavoring agents in food and beverages worldwide.In China,ginger is one of the medicine homologous resources prescribed by the ministry of Health of China.In the recent years,it has been widely used for the prevention and treatment of gastrointestinal disorders,cardiovascular disease,cancers and other diseases.6-Shogaol is one of the active ingredients in ginger,although studied as one of the antitumor phytochemicals but its in-depth anti-cancer mechanisms still remain unexplored against human endometrial cancer cells.The main research methods,contents and results are revealed follows:（1）Promotion of apoptotic mechanism of 6-shogaol on human endometrial cancer cell line Ishikawa cell.MTT and cell cycle experiments showed that 6-shogaol could inhibit Ishikawa cells proliferation at IC₅₀（24.91μM）with cell cycle arrest in the G2/M phase.Moreover,it promoted apoptosis as a result triggered ROS production,then activated key ER response biomarkers in Ishikawa cell associated with mitochondria,and ultimately modulated the regulation of related genes and proteins,like ATF-6,IRE1α,Chop,Bcl-2,Caspase-9,Caspase-3 and PARP.（2）Inhibitory effects of 6-shogaol on autophagic and metastatic mechanism in human endometrial cancer cells.Cell wound healing and Transwell experiments showed that 6-shogaol could triggered some autophagy biomarkers like mTOR,p62,Beclin-1,and LC3B.Moreover,some metastasis biomarkers associated with PI3K/AKT/MAPK signaling pathways were also influenced by 6-shogaol treatment,like MMP2,MMP9,E-cadherin,N-cadherin,etc.（3）The inhibition effect of 6-shogaol on tumor xenograft nude mice models.Tumor volume was inhibited significantly in treated group compared with control group and the inhibition ratio was 58.12%.Some proteins related with proliferation,apoptosis,autophagy,and metastasis were influenced by 6-shogaol treatment,like Ki-67,Bcl-2,Chop,Beclin-1,LC3B,MMP2,MMP9,etc.Moreover,NF-κB signaling pathway was influenced by 6-shogaol treatment,which indicated that 6-shogaol can also exert an in vivo anti-inflammatory effect.