Homoharringtonine induced immune alteration for an Efficient Anti-tumor Response in Mouse Models of Non-small Cell Lung Adenocarcinoma Expressing Kras Mutation

doi:10.1038/s41598-018-26454-w

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標題:	Homoharringtonine induced immune alteration for an Efficient Anti-tumor Response in Mouse Models of Non-small Cell Lung Adenocarcinoma Expressing Kras Mutation
作者:	Weng, Tzu-Yang Wu, Hsuan Franziska Li, Chung-Yen Hung, Yu-Hsuan Chang, Yu-Wei Chen, Yi-Ling Hsu, Hui-Ping Chen, Yu-Hung Wang, Chih-Yang Chang, Jang-Yang Lai, Ming-Derg
貢獻者:	Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg Natl Cheng Kung Univ, Dept Med Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management Natl Hlth Res Inst, Natl Inst Canc Res
關鍵字:	Antigen-Presenting Cells B-Cells Translational Control Myeloid-Leukemia Stat3 Activation Signal Pathway In-Vitro Cancer Apoptosis Chemotherapy
日期:	2018-05-29
上傳時間:	2019-11-15 15:47:02 (UTC+8)
出版者:	NATURE PUBLISHING GROUP
摘要:	Homoharringtonine (HHT), an inhibitor of protein synthesis, has been used to treat leukemia. Its therapeutic effects on non-small cell lung adenocarcinoma carrying KRAS mutation and their immune system are less understood. The present study examined the therapeutic efficacy and the immune effects of HHT in two murine lung tumor models, xenograft and transgenic, carrying the Kras mutation G12D and G12C respectively. HHT exhibited efficient anticancer activity, significantly suppressing lung tumor growth in vitro and in vivo. The levels of 22 cytokines and chemokines in splenocytes of tumor-bearing mice were examined. Interleukin-12 expression was lower in splenocytes of HHT-treated mice when compared to the controls as demonstrated by a cytokine array and an enzyme-linked immunosorbent assay. The expression levels of CD80, CD86, and CD69 in B220(+) B cells from splenocytes of HHT-treated mice were higher than that of control mice in two mouse tumor models. Furthermore, antitumor effect of HHT was attenuated with depletion of B cells. Increased numbers of CD80(+) and CD86(+) B cells were observed in the mice treated with narciclasine, another translation inhibitor. In conclusion, HHT changed the features of immune cells, and exhibited efficient anti-tumor activity against lung tumor carrying mutant Kras expression.
link:	http://dx.doi.org/10.1038/s41598-018-26454-w
關聯:	Scientific Reports, v.8, 8216
顯示於類別:	[高齡福祉養生管理系] 期刊論文

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