Synergistic effect of sodium butyrate and oxaliplatin on colorectal cancer

• Published in: Translational oncology Vol. 27; p. 101598
• Main Authors: Shuwen, Han, Yangyanqiu, Wang, Jian, Chu, Boyang, Hu, Gong, Chen, Jing, Zhuang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023; Elsevier
• Subjects: Clinical adjuvant; Colorectal cancer; Oxaliplatin; Sodium butyrate; Synergistic effect; NCCN; CRT; OS; Colorectal cancer; ICD; SCFA; NaB; DFS; Sodium butyrate; Oxaliplatin; CRC; mCRC; OXA; CCK-8; PD-L2; Clinical adjuvant; Synergistic effect; DACH; GC/MS; HMGB-1; DC
• DOI: 10.1016/j.tranon.2022.101598
• ISSN: 1936-5233

•NaB was a differential metabolite that affected the efficacy of OXA.•NaB can inhibit the proliferation, invasion and migration and induce the apoptosis of CRC cells.•Sodium butyrate combined with oxaliplatin has synergistic effect on CRC cells. Oxaliplatin (OXA) is a chemotherapy agent commonly used in the treatment of colorectal cancer (CRC). Sodium butyrate (NaB) has an antitumor effect. In total, 30 patients in stage III who completed 8 cycles of chemotherapy regimens were recruited for this study. The patients were divided into good and bad groups based on the chemotherapy efficacy. Gas chromatography–mass spectrometry (GC/MS) was used to detect microbial metabolites in stool samples from CRC patients. Cell counting kit-8 (CCK-8), Annexin-V APC/7-AAD double staining, Transwell assays, scratch-wound assays, and EdU assays were used to detect cell proliferation, apoptosis, invasion and migration, respectively. Fluoroelectron microscopy was used to observe the cell structures. To verify the inhibitory effect of NaB and OXA at animal level, a subcutaneous transplanted tumor model was established. Finally, 16S sequencing technology was used to detect intestinal bacteria. GC–MS was used to detect metabolites in mouse stools. NaB was a differential metabolite that affected the efficacy of OXA. NAB and oxaliplatin can synergically inhibit cell proliferation, migration and invasion, and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of oxaliplatin and sodium butyrate on tumor in mice. In addition, the intestinal microbe detection and microbial metabolite detection in fecal samples from mice showed significant differences between butyrate-producing bacteria and NaB. NaB and OXA can synergistically inhibit the proliferation, invasion and metastasis of CRC cells and promote the apoptosis of CRC cells. NaB, as an OXA synergist, has the potential to become a new clinical adjuvant in CRC chemotherapy.