| Autor: |
Chang WK; Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, Taiwan.; Department of Medicine, MacKay Medical College, New Taipei 252, Taiwan., Chen YT; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, Taiwan.; Department of Medicine, MacKay Medical College, New Taipei 252, Taiwan., Lin CP; Department Medical Research, MacKay Memorial Hospital, New Taipei City 251, Taiwan., Wang CJ; Department Medical Research, MacKay Memorial Hospital, New Taipei City 251, Taiwan., Shieh HR; Department Medical Research, MacKay Memorial Hospital, New Taipei City 251, Taiwan., Chi CW; Department Medical Research, MacKay Memorial Hospital, New Taipei City 251, Taiwan., Tsai TH; Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.; Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan.; Department of Chemistry, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.; School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Chen YJ; Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.; Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.; Department of Radiation Oncology, MacKay Memorial Hospital, Taipei 104, Taiwan. |
| Abstrakt: |
Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of mRNA and protein were assessed. A syngeneic animal model was established by implanting CT26 cells into BALB/c mice for in vivo experiments. Multi-parameter flow cytometry was used to analyze the splenic cell lineages and tumor microenvironment (TME). The in vitro data revealed that cordycepin, but not adenosine, inhibited CT26 cell viability. The protein, but not mRNA, expression levels of A2AR and A2BR were suppressed by cordycepin but not by adenosine in CT26 cells. The combination of cordycepin, but not adenosine, with anti-PD1 exhibited a greater tumor-inhibitory effect than anti-PD1 alone as well as inhibited the expression of A2AR and A2BR in splenic macrophages. In the TME, the combination of cordycepin and anti-PD1 increased the number of CD3+ T cells and neutrophils and decreased the number of natural killer (NK) cells. Overall, cordycepin augmented the antitumor effects of anti-PD1 against mouse colon carcinoma cells and inhibited the expression of the adenosine receptors A2AR and A2BR in splenic macrophages and intratumoral NK cells. |
