Primary study of the effects of ursolic acid on colorectal tumor and tumor microenvironment in mice

Abstract

Objective To investigate the effect of ursolic acid (UA) on the colorectal tumor and microenvironment in mice, and to provide a theoretical basis for the clinical application of UA. Methods The models of subcutaneous transplanted tumor of mouse CT26 cells was established. The models were divided into four groups: control group, tumor bearing group, tumor bearing dimethyl sulfoxide (DMSO) group and tumor bearing UA group. The serum levels of interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA). The number and percentage of myeloid-derived suppressor cell (MDSC) in the spleen of mice were analyzed by flow cytometry. The mRNA levels of IL-6 and signal transducer and activator of transcription 3 (STAT3) in tumor were examined by real-time quantitative polymerase chain reaction (RT-PCR). The protein levels of STAT3 and p-STAT3 in tumor were detected by Western blotting. Results The results showed that UA could significantly decrease the number of spleen MDSC. The accounts of spleen MDSC of tumor bearing UA group (249.60±17.12) was lower than that of tumor bearing DMSO group (366.40±34.08), and the difference was statistically significant (P=0.021). The serum level of IL-6 in tumor bearing UA group [(46.40±17.05) pg/ml] was decreased than that in tumor bearing DMSO group [(94.27±21.51) pg/ml], and the difference was statistically significant (P=0.012). The expression levels of IL-6 and STAT3 mRNA in tumor tissues of tumor bearing UA group (0.12±0.01, 0.21±0.08) were lower than those of tumor bearing DMSO group (0.69±0.14, 0.79±0.06), and the differences were statistically significant (P=0.008; P=0.003). The protein expression levels of STAT3 and p-STAT3 in tumor tissues of tumor bearing UA group (0.81±0.02, 0.28±0.04) were lower than those of tumor bearing DMSO group (0.98±0.02, 0.91±0.22), and the differences were statistically significant (P=0.027; P=0.029) . Conclusion UA may inhibit the activation of STAT3 signaling pathway and the amplification of MDSC in microenvironment by redu-cing IL-6, thus to enhance the function of immune-killing tumor cells to regulate tumor immune microenvironment and inhibit the immune escape of mouse colorectal cancer cells. Key words: Ursolic acid; Colorectal neoplasms; Tumor microenvironment; Myeloid-derived suppre-ssor cells