关键词: Apoptosis Celastrol Cell cycle regulation Gastric cancer Synergism Terpenoid

Mesh : Humans Pentacyclic Triterpenes / pharmacology Fluorouracil / pharmacology Stomach Neoplasms / drug therapy pathology metabolism Apoptosis / drug effects Cell Proliferation / drug effects Cell Line, Tumor Triterpenes / pharmacology Drug Synergism Antineoplastic Combined Chemotherapy Protocols / pharmacology Cell Cycle / drug effects

来  源:   DOI:10.32604/or.2024.047187   PDF(Pubmed)

Abstract:
UNASSIGNED: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257).
UNASSIGNED: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry.
UNASSIGNED: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 μM for celastrol, 20.7 and 11.6 μM for 5-FU, and 5.03 and 4.57 μM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.
UNASSIGNED: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.
摘要:
尽管有5-氟尿嘧啶(5-FU)等化疗药物,由于耐药性和副作用,一些癌症如胃癌的治疗仍然具有挑战性。本研究旨在探讨雷公藤红素联合化疗药物5-FU对人胃癌细胞株(AGS和EPG85-257)增殖及诱导凋亡的影响。
在这项体外研究中,用不同浓度的雷公藤红素处理AGS和EPG85-257细胞,5-FU,和他们的组合。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)测定法评估细胞增殖。使用Compusyn软件研究了5-FU和雷公藤红素的协同作用。使用流式细胞术测量细胞周期不同阶段的DNA含量和凋亡率。
与低浓度(10%抑制浓度(IC10))的雷公藤红素和5-FU共同处理显着降低了IC50(p<0.05),因此治疗后48小时,celastrol的IC50计算为3.77和6.9μM,5-FU为20.7和11.6μM,对于AGS和EPG85-257细胞,它们的组合为5.03和4.57μM,分别。用雷公藤红素处理的AGS细胞的平均凋亡百分比,5-FU,并且它们的组合分别获得23.9、41.2和61.9,对于EPG85-257细胞分别获得5.65、46.9和55.7。此外,5-FU和celastrol-5-FU组合在合成阶段诱导细胞周期停滞。
尽管雷公藤红素可以降低5-氟尿嘧啶的浓度,足以抑制胃癌细胞,需要进一步的研究才能得出关于雷公藤多酚抗癌作用的确凿证据。
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