一种新型鞘磷脂类似物在化疗敏感和化疗耐药乳腺癌中的抗癌效果。
Anti-cancer effectiveness of a novel ceramide analog on chemo-sensitive and chemo-resistant breast cancers.
发表日期:2023 Aug 15
作者:
Tulasi Ponnapakkam, Tyjah Saulsberry, Miriam Hill-Odom, Teresa Beamon, Royce Hooks, Navneet Goyal, Shahensha Shaik, Muralidharan Anbalagan, Maryam Foroozesh
来源:
Cellular & Molecular Immunology
摘要:
酯脂醇已被证明具有抗癌活性。作为寻找更有效的乳腺癌治疗方法的一个更大研究的一部分,新型酯脂醇类似物(S,E)-3-羟基-2-(2-羟基苯基亚甲基)氨基-N-十四烷基丙酰胺(类似物315)被研发出来。为了评估类似物315在体外乳腺癌细胞中是否表现出下列任何或组合性能:抑制增殖、诱导凋亡和改变蛋白表达。此外,还要确定类似物315是否在小鼠体内抑制化疗抵抗性乳腺癌肿瘤的生长。体外实验中分别评估了类似物315处理后在三个乳腺癌细胞株(MCF-7、MCF-7TN-R和MDA-MB-231)中的细胞增殖和凋亡情况,并作出了报告。蛋白质表达通过微阵列分析进行了评估。对于体内实验,化疗抵抗性乳腺癌细胞用于两组小鼠(处理组和对照组)的肿瘤发展。类似物315(每天25毫克/千克)或对照(二甲基亚砜)通过腹腔注射给予小鼠连续7天。报道了类似物315对抑制化疗抵抗性乳腺癌肿瘤生长的影响。类似物315减少了MCF-7TN-R化疗抵抗性肿瘤的负担(体积和重量)。对照组的小鼠观察到了肝转移,而治疗组的动物则没有。Ki-67作为乳腺癌细胞增殖标记物,在对照肿瘤组织中显著增加(P < 0.05)。体外研究显示类似物315在所有研究的三个乳腺癌细胞株中抑制了细胞增殖,改变了蛋白质表达并诱导了细胞凋亡,其中对MCF-7TN-R细胞的影响最为显著。类似物315减少了化疗抵抗性乳腺癌的肿瘤生长,抑制了细胞增殖,改变了蛋白质表达并诱导了细胞凋亡。版权所有©2023 Wolters Kluwer Health, Inc. 保留所有权利。
Ceramides are known to show anti-cancer activity. A novel ceramide analog, (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)amino-N-tetradecylpropanamide (analog 315) was developed as part of a larger study focused on finding more effective breast cancer treatments.To assess whether analog 315 shows any or a combination of the following effects in breast cancer cells in vitro: inhibiting proliferation, inducing apoptosis, and altering protein expression. Also, to determine whether it inhibits chemo-resistant breast cancer tumor growth in vivo mouse model.In vitro cell proliferation and apoptosis after treatment with analog 315 were assessed in three breast cancer cell lines (MCF-7, MCF-7TN-R, and MDA-MB-231) and reported. Protein expression was assessed by microarray assay. For the in vivo studies, chemo-resistant breast cancer cells were used for tumor development in two groups of mice (treated and control). Analog 315 (25 mg/kg/day) or control (dimethyl sulfoxide) was administered intraperitoneally for 7 days. Effects of analog 315 on inhibiting the growth of chemo-resistant breast cancer tumors after treatment are reported.Analog 315 reduced MCF-7TN-R chemo-resistant tumor burden (volume and weight) in mice. Liver metastasis was observed in control mice, but not in the treated animals. Ki-67, a proliferation marker for breast cancer cells, increased significantly (P < 0.05) in control tumor tissue. In vitro studies showed that analog 315 inhibited cell proliferation, altered protein expression and induced apoptosis in all three breast cancer cell lines studied, of which the effects on MCF-7TN-R cells were the most significant.Analog 315 reduced tumor growth in chemo-resistant breast cancer, inhibited cell proliferation, altered protein expression, and induced apoptosis in all three cell lines studied.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.