[目的]探讨GPR109A介导的短链脂肪酸摄入对结直肠癌细胞增殖的潜在机制。[方法]纳入2020年9月-2023年1月收治的结直肠癌患者45例以及相同例数的同时期体检的健康志愿者，收集结直肠癌患者和健康志愿者的粪便并提取短链脂肪酸(SCFAs)。不同来源的SCFAs处理后检测结直肠癌细胞HCT116或HT29的增殖水平。检测不同来源SCFAs中PA、BA、ISO-BA、2M-BA的水平。敲低或过表达GPR109A后检测结直肠癌细胞的增殖水平以及短链脂肪酸PA、BA、ISO-BA、2M-BA的摄入水平。[结果]相比于结直肠癌患者，健康志愿者粪便中的SCFAs短链脂肪酸水平更高(174 023。38±1 435。92 vs 18 372±1 382。50，P＜0。05)、抑制结直肠癌细胞效果更明显(1。41±0。08 vs2。42±0。10，P＜0。05)、使 GPR109A 表达水平上升更多(0。73±0。07 vs 0。30±0。02，P＜0。05)。短链脂肪酸处理后结直肠癌细胞的增殖水平显著下降(2。88±0。09 vs 1。48±0。08，P＜0。05)。过表达GPR109A后结直肠癌细胞的增殖水平显著下降(2。56±0。12 vs 1。22±0。08，2。64±0。11 vs 1。38±0。08，P＜0。05)。过表达 GPR109A 后，结直肠癌细胞中短链脂肪酸水平上升(100。00±2。58 vs 350。34±37。15，P＜0。05)。[结论]GPR109A介导了结直肠癌细胞中短链脂肪酸的摄入，并且摄入的短链脂肪酸PA、BA、ISO-BA、2M-BA能够显著抑制结直肠癌细胞的增殖。
GPR109A regulates the proliferative effect of short-chain fatty acid intake on colorectal cancer cells
[Objective]To investigate the potential mechanism of GPR109A-mediated short-chain fatty acid intake on the proliferation of colorectal cancer cells.[Method]A total of 45 patients with colorectal cancer admitted from September 2020 to January 2023 and the same number of healthy volunteers who underwent physical examination during the same period were in-cluded.Stool of both patients with colorectal cancer and healthy volunteers was collected and short-chain fatty acids(SCFAs)were extracted.The proliferation levels of colorectal cancer cells HCT116 or HT29 were detected after treatment of SCFAs from different sources.The levels of PA,BA,ISO-BA,and 2M-BA in SCFAs from different sources were detected.The prolifera-tion levels of colorectal cancer cells and the uptake levels of short-chain fatty acids PA,BA,ISO-BA,and 2M-BA were de-tected after knockdown or overexpression of GPR109A.[Result]Compared with colorectal cancer patients,SCFAs in the stool of healthy volunteers had higher levels of short-chain fatty acids(174 023.38±1 435.92 vs 18 372±1 382.50,P＜0.05),in-hibited colorectal cancer cells more effectively(1.41±0.08 vs 2.42±0.10,P＜0.05),and increased GPR109A expression level(0.73±0.07 vs 0.30±0.02,P＜0.05).The proliferation level of colorectal cancer cells was significantly decreased af-ter short-chain fatty acid treatment(2.88±0.09 vs 1.48±0.08,P＜0.05).The proliferation level of colorectal cancer cells was significantly decreased after overexpression of GPR109A(2.56±0.12 vs 1.22±0.08,2.64±0.11 vs 1.38±0.08,P＜0.05).The level of short-chain fatty acids in colorectal cancer cells increased after overexpression of GPR109A(100.00±2.58 vs 350.34±37.15,P＜0.05).[Conclusion]GPR109 A mediated the uptake of short-chain fatty acids in colorectal canc-er cells,and the ingested short-chain fatty acids PA,BA,ISO-BA,and 2M-BA were able to significantly inhibit the prolif-eration of colorectal cancer cells.
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