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

Scientific Reports
Tzu-Yang WengMing-Derg Lai

Abstract

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 ...Continue Reading

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Citations

Jan 14, 2020·Journal of Chemotherapy·Xue-Jun WangMei-Juan Yan
Jan 7, 2021·Antioxidants & Redox Signaling·Emiliano Panieri, Luciano Saso
Jul 22, 2021·Cancer Cell International·Yanming LuoHaiyang Yu
Jan 10, 2020·Journal of Natural Products·Feng LiuYuanqiang Guo
Jul 24, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jyoti SinghAbha Meena

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
PCR
flow cytometry
transgenic
xenograft
protein assay
X-ray

Software Mentioned

GraphPad Prism
ImageJ

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