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泰国诺丽果汁乙醇提取物与5-氟尿嘧啶联合应用对胆管癌细胞的体内外抗癌作用

Anticancer effects of the combined Thai noni juice ethanolic extracts and 5-fluorouracil against cholangiocarcinoma cells in vitro and in vivo.

作者信息

Prompipak Jeerati, Senawong Thanaset, Sripa Banchob, Ketterman Albert J, Utaiwat Suppawit, Woranam Khanutsanan, Jeeunngoi Jarckrit, Senawong Gulsiri

机构信息

Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, 40002, Thailand.

Natural Product Research Unit, Faculty of Science, Khon Kaen University, Khon Kaen, 40002, Thailand.

出版信息

Sci Rep. 2021 Jul 21;11(1):14866. doi: 10.1038/s41598-021-94049-z.

DOI:10.1038/s41598-021-94049-z
PMID:34290264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8295291/
Abstract

Application of 5-fluorouracil (5-FU) in cholangiocarcinoma (CCA) is limited by adverse side effects and chemoresistance. Therefore, the combination therapy of 5-FU with other substances, especially natural products may provide a new strategy for CCA treatment. The aim of this study was to evaluate the combination effects of 5-FU and two ethanolic extracts of Thai noni juice (TNJ) products on CCA cell lines and nude mice xenografts. The results of antiproliferative assay showed the combination treatment of 5-FU and each TNJ ethanolic extract exerted more cytotoxicity on CCA cells than either single agent treatment. Synergistic effects of drug combinations can enable the dose reduction of 5-FU. The mechanism underlying a combination treatment was apoptosis induction through an activation of p53 and Bax proteins. In the nude mouse xenograft model, combination treatments of 5-FU with each TNJ ethanolic extract suppressed the growth of CCA cells implanted mice more than single agent treatments with no effects on mouse body weight, kidney, and spleen. Moreover, low doses of TNJ ethanolic extracts reduced the hepatotoxicity of 5-FU in nude mice. Taken together, these data suggested that the ethanolic extracts of TNJ products can enhance the anti-CCA effect and reduce toxicity of 5-FU.

摘要

5-氟尿嘧啶（5-FU）在胆管癌（CCA）中的应用受到不良副作用和化疗耐药性的限制。因此，5-FU与其他物质，尤其是天然产物的联合治疗可能为CCA治疗提供新策略。本研究旨在评估5-FU与两种泰国诺丽果汁（TNJ）乙醇提取物对CCA细胞系和裸鼠异种移植瘤的联合作用。抗增殖试验结果表明，5-FU与每种TNJ乙醇提取物联合处理对CCA细胞的细胞毒性比单一药物处理更强。药物组合的协同作用可使5-FU剂量降低。联合治疗的潜在机制是通过激活p53和Bax蛋白诱导细胞凋亡。在裸鼠异种移植瘤模型中，5-FU与每种TNJ乙醇提取物联合处理比单一药物处理更能抑制植入小鼠体内的CCA细胞生长，且对小鼠体重、肾脏和脾脏无影响。此外，低剂量的TNJ乙醇提取物可降低5-FU对裸鼠的肝毒性。综上所述，这些数据表明TNJ产品的乙醇提取物可增强抗CCA作用并降低5-FU的毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/655d0e66865a/41598_2021_94049_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/2f8ace8ce1fa/41598_2021_94049_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/28657d8059c3/41598_2021_94049_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/e5c79c5d2063/41598_2021_94049_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/655d0e66865a/41598_2021_94049_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/2f8ace8ce1fa/41598_2021_94049_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/f07845c4317b/41598_2021_94049_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/4d1c4a436e23/41598_2021_94049_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/28657d8059c3/41598_2021_94049_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/74130a9579ad/41598_2021_94049_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/e5c79c5d2063/41598_2021_94049_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5b/8295291/655d0e66865a/41598_2021_94049_Fig7_HTML.jpg

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