| Autor: |
Weng TY; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Wu HF; Department of Medicine, National Cheng Kung University, Tainan, Taiwan., Li CY; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Hung YH; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Chang YW; Department of Medicine, National Cheng Kung University, Tainan, Taiwan., Chen YL; Department of Senior Citizen Services Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan., Hsu HP; Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Chen YH; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Medicine, National Cheng Kung University, Tainan, Taiwan., Wang CY; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Chang JY; National Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan., Lai MD; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. a1211207@mail.ncku.edu.tw. |
| Abstrakt: |
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. |
