Oxymatrine suppresses colorectal cancer by regulating intestinal flora in mice / 肿瘤研究与临床

ABSTRACT

Objective:To explore the effect of oxymatrine on the intestinal flora of mice with colorectal cancer and its related microbial mechanisms.Method:Based on azoxymethane (AOM)-dextran sulfate sodium (DSS) method, 16 5-week-old male BALB/c mice were performed to establish a orthotopic colorectal tumor mouse model. According to the stratified sampling method, mice were divided into the control group and oxymatrine intervention group, 8 in each group. From 5th week, mice in oxymatrine intervention group were given intraperitoneal injection of 10 mg/kg oxymatrine solution every other day; mice in the control group were given the same amount of 0.9% NaCl injection intraperitoneally until the end of the experiment at 81st d of modeling. The body weight of mice was measured every 3 days since the beginning of the modeling; before mice were sacrificed, mouse feces were collected for microbiological and 16S ribosome (rDNA) high-throughput sequencing. The tumor number of colorectal cancer was observed and tumor tissues were taken out. Hematoxylin and eosin (HE) staining was used to evaluate the differentiation degree, the percentage of tumor tissues with all differentiation degrees in the total tumor tissues was calculated, and immunohistochemistry staining was used to test the expression of Ki-67.Results:At the late of the experiment (d 49-d 81 of modeling), the body weight of mice in the control group was lower than that of mice in oxymatrine intervention group [modeling at 81st d (22.9±0.5) g vs. (24.0±0.5) g, t=2.187, P < 0.05], and the tumor number of intestinal tract in oxymatrine intervention group was lower than that in the control group [(8.5±1.2) vs. (12.0±1.2), t = 2.824, P < 0.05] at the end of experiment. The percentage of well-differentiated tumors in mice intestinal tract in the oxymatrine intervention group was higher than that of mice in the control group [(62.5±3.7)% vs. (25.0±2.6)%], and the expression score of Ki-67 in oxymatrine intervention group was lower compared with that in the control group [(3.2±1.0) scores vs. (6.0±1.0) scores, t = 2.668, P < 0.05). At the phylum level, the abundance of Firmicutes and Proteobacteria in the intestine of mice in oxymatrine intervention group was higher than that in the control group (all P < 0.05), the abundance of Bacteroides in oxymatrine intervention group was lower than that in the control group ( P = 0.037). At the genus level, compared with the control group, the oxymatrine intervention group had a higher abundance of norank_f__Muribaculaceae ( P = 0.001). The abundance of Bacteroides, Odoribacter, Parabacteroides and alloprevotella in oxymatrine intervention group was lower than that in the control group (all P < 0.05). Conclusion:Oxymatrine can decrease the incidence of colorectal cancer in mice and delay development of colorectal cancer by regulating the gut microbiota and sustaining the stability of intestinal flora.