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重组人乳铁蛋白增强载实体埃利希腹水癌小鼠的表阿霉素化疗。

Recombinant Human Lactoferrin Augments Epirubicin Chemotherapy in Solid Ehrlich Carcinoma Bearing Mice.

机构信息

Biochemistry Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Ministry of Health, Dakahleya, Egypt.

出版信息

Curr Drug Saf. 2023;18(3):345-354. doi: 10.2174/1574886317666220429102445.

Abstract

BACKGROUND

Lactoferrin (LF) is a member of the transferrin family, which is known for its immunomodulatory properties. LF has been widely used as an anticancer medication in various cancers including breast cancer.

AIMS

The current study aimed to examine the molecular mechanisms underlying the therapeutic potential of recombinant human lactoferrin (rhLF), either alone or combined with epirubicin (EPI), in mice bearing solid Ehrlich carcinoma (SEC).

METHODS

SEC-bearing female mice (n=40) were divided into 4 equal groups. Mice were given rhLF orally (100mg/kg/mouse) daily and/or EPI i.p (8mg/kg/mouse). The experiment lasted 14 days, after which samples were collected to measure IL-18 and phosphorylated c-Jun N-terminal kinase (p-JNK) by ELISA and p gene expression by real-time PCR.

RESULTS

Administration of rhLF, either alone or combined with EPI, markedly decreased the tumor volume and increased tumor inhibition rate as well as survival rate compared to either tumor control group or EPI-mono treated group. In addition, co-administration of rhLF and EPI increased the level of activated JNKs and expression of p in tumor tissues compared to the tumor, control group, exhibiting their pro-apoptotic properties. Moreover, the combined treatment with rhLF and EPI elevated IL-18 level in the intestinal mucosa compared to other experimental groups with a possible immune-enhancing effect.

CONCLUSION

Recombinant human lactoferrin exhibited potential anticancer and immune-enhancing properties in mice with breast cancer. Co-treatment with rhLF and EPI proved to be a promising strategy in cancer treatment.

摘要

背景

乳铁蛋白(LF)是转铁蛋白家族的一员,以其免疫调节特性而闻名。LF 已被广泛用作包括乳腺癌在内的各种癌症的抗癌药物。

目的

本研究旨在探讨重组人乳铁蛋白(rhLF)单独或联合表阿霉素(EPI)治疗荷实体 Ehrlich 癌(SEC)小鼠的治疗潜力的分子机制。

方法

将 40 只荷 SEC 雌性小鼠分为 4 组,每天口服 rhLF(100mg/kg/只)和/或腹腔注射 EPI(8mg/kg/只)。实验持续 14 天,收集样本通过 ELISA 检测白细胞介素 18(IL-18)和磷酸化 c-Jun N 端激酶(p-JNK),通过实时 PCR 检测 p 基因表达。

结果

与肿瘤对照组或 EPI 单药治疗组相比,rhLF 单独或联合 EPI 给药可显著降低肿瘤体积,提高肿瘤抑制率和存活率。此外,rhLF 和 EPI 联合给药可增加肿瘤组织中激活的 JNKs 和 p 的表达,表现出其促凋亡特性。此外,rhLF 和 EPI 的联合治疗可提高肠黏膜中的 IL-18 水平,具有潜在的免疫增强作用。

结论

重组人乳铁蛋白在荷乳腺癌小鼠中表现出潜在的抗癌和免疫增强特性。rhLF 和 EPI 的联合治疗被证明是一种有前途的癌症治疗策略。

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