Plasmodium infection suppresses colon cancer growth by inhibiting proliferation and promoting apoptosis associated with disrupting mitochondrial biogenesis and mitophagy in mice

Parasites & Vectors

Runqi Fang¹  Jingxiang Xu¹  Dianyi Chen¹  Yuanxia Xu¹  Jiangyan Li²  Qiang Fang³  Zhiyong Tao³  Xin Yao³  Yujie Cao³  Hui Xia³  Li Lu⁴  Hao Chen⁵  Chuanqi Liu⁵  Kexue Wang⁵ 

[1] Clinical Medical Department, Bengbu Medical College;Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College;Department of Microbiology and Parasitology, Bengbu Medical College;School of Fundamental Sciences, Bengbu Medical College;School of Life Sciences, Bengbu Medical College;

关键词: Plasmodium;    Colon cancer;    Mitochondrial apoptosis;    Mitophagy;    Mitochondrial biogenesis;   

DOI  :  10.1186/s13071-022-05291-x

来源: DOAJ

【 摘 要 】

Abstract Background Colon cancer is a common gastrointestinal tumor with a poor prognosis, and thus new therapeutic strategies are urgently needed. The antitumor effect of Plasmodium infection has been reported in some murine models, but it is not clear whether it has an anti-colon cancer effect. In this study, we investigated the anti-colon cancer effect of Plasmodium infection and its related mechanisms using a mouse model of colon cancer. Methods An experimental model was established by intraperitoneal injection of Plasmodium yoelii 17XNL-infected erythrocytes into mice with colon cancer. The size of tumors was observed dynamically in mice, and the expression of Ki67 detected by immunohistochemistry was used to analyze tumor cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and the expression of apoptosis-related proteins including Bax, Bcl-2, caspase-9, and cleaved caspase-3 was detected by western blot and immunohistochemistry, respectively. Transmission electron microscopy (TEM) was used to observe the ultrastructural change in colon cancer cells, and the expression of mitochondrial biogenesis correlative central protein, PGC-1α, and mitophagy relevant crucial proteins, PINK1/Parkin, were detected by western blot. Results We found that Plasmodium infection reduced the weight and size of tumors and decreased the expression of Ki67 in colon cancer-bearing mice. Furthermore, Plasmodium infection promoted mitochondria-mediated apoptosis in colon cancer cells, as evidenced by the increased proportion of TUNEL-positive cells, the upregulated expression of Bax, caspase-9, and cleaved caspase-3 proteins, and the downregulated expression of Bcl-2 protein. In colon cancer cells, we found destroyed cell nuclei, swollen mitochondria, missing cristae, and a decreased number of autolysosomes. In addition, Plasmodium infection disturbed mitochondrial biogenesis and mitophagy through the reduced expression of PGC-1α, PINK1, and Parkin proteins in colon cancer cells. Conclusions Plasmodium infection can play an anti-colon cancer role in mice by inhibiting proliferation and promoting mitochondria-mediated apoptosis in colon cancer cells, which may relate to mitochondrial biogenesis and mitophagy. Graphical Abstract

【 授权许可】

Unknown