Translational Pharmacy Center of Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Laboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, Zhejiang 310053, China.
Translational Pharmacy Center of Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Food Res Int. 2021 Mar;141:110147. doi: 10.1016/j.foodres.2021.110147. Epub 2021 Jan 18.
Researches demonstrated that gut microbiota are associated with breast cancer progression. This study aims to evaluate the anti-breast tumor effects of daucosterol linolenate (DLA), daucosterol linoleate (DL), and daucosterol palmitate (DP) from sweet potato in MCF-7 xenograft nude mice by determining the tumor growth, serum tumor markers, tumor-related proteins, and performing 16S rDNA sequencing. After treatment at 87.8 mg/kg/day for 29 days, DLA, DL and DP delayed tumor growth and decreased levels of tumor marker carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 153 (CA153) in vivo. All treatments activated caspase 3, 9, PARP1 cleavage, down-regulated Ki67, VEGF, BCL-2, BCL-XL, up-regulated BAX expression, and inhibited PI3K/AKT/NF-κB activation in tumor tissues. Their anti-breast tumor effects were associated with the regulation on gut microbiota. The three treatments increased Bacteroidetes whereas decreased Firmicutes richness. They also modulated the diversity of gut microbiota at family and genus levels. Furthermore, DL treatment promoted butyric acid secretion, DP promoted acetic acid and butyric acid secretion in the colorectal and feces. Our findings indicate that DLA, DL, and DP inhibit tumor growth in MCF-7 xenograft nude mice by regulating the homeostasis of gut microbiota, producing SCFAs, and then disturbing the expression of cancer-related proteins. The present study suggests three phytosterols as gut microbiota regulator for breast cancer prevention.
研究表明，肠道微生物群与乳腺癌的进展有关。本研究旨在通过测定肿瘤生长、血清肿瘤标志物、肿瘤相关蛋白，并进行 16S rDNA 测序，评估来自甘薯的芝麻甾醇亚麻酸（DLA）、芝麻甾醇亚油酸（DL）和芝麻甾醇棕榈酸（DP）对 MCF-7 异种移植裸鼠的抗乳腺癌作用。在 87.8mg/kg/天治疗 29 天后，DLA、DL 和 DP 延迟了肿瘤生长，并降低了体内肿瘤标志物癌胚抗原（CEA）、癌抗原 125（CA125）和癌抗原 153（CA153）的水平。所有治疗均激活了 caspase 3、9、PARP1 裂解，下调了 Ki67、VEGF、BCL-2、BCL-XL 的表达，上调了 BAX 的表达，并抑制了肿瘤组织中 PI3K/AKT/NF-κB 的激活。它们的抗乳腺癌作用与对肠道微生物群的调节有关。三种处理方法增加了拟杆菌门，而减少了厚壁菌门的丰富度。它们还调节了肠道微生物群在科和属水平上的多样性。此外，DL 处理促进了丁酸的分泌，DP 促进了乙酸和丁酸在结直肠和粪便中的分泌。我们的研究结果表明，DLA、DL 和 DP 通过调节肠道微生物群的平衡、产生 SCFAs，然后干扰与癌症相关的蛋白表达，抑制 MCF-7 异种移植裸鼠的肿瘤生长。本研究表明，三种植物甾醇可作为预防乳腺癌的肠道微生物群调节剂。
