Background

Individual treatment with either the standard chemotherapeutic drug tamoxifen (Tam), the natural product hesperidin (Hes), or camel milk exosomes (Exo) has been shown to inhibit breast cancer MCF7 cells proliferation. However, little is known regarding their combined effect on MCF7 both in vitro and in vivo.

Objective

This study aimed to investigate whether the combined therapy of Tam, Hes, and Exo could synergistically inhibit the proliferation of MCF7 both in vitro and in vivo and could decrease Tam side effects.

Results

Combined treatment with Tam, Hes, and Exo significantly inhibited MCF7 proliferation as compared to the individual treatment. This cotreatment also had higher apoptotic, anti-migratory, and anti-invasive effects against MCF7 than individual treatment as revealed by; (1) Bax and caspase3 upregulation and Bcl2 downregulation; (2) downregulation of breast cancer-related genes (EGFR and ERα); (3) downregulation of MMP9 and upregulation of TIMP1; and (4) decreased number of migratory cells (transwell assay). This therapeutic potential was confirmed by the results of the in vivo study (mouse model of breast cancer induced by MCF7 xenograft). Cotreated mice had the smallest tumor size, highest Bax and caspase3, lowest Bcl2 and VEGF expression in the xenograft. This cotreatment was safer and reduced Tam side effects as revealed by; (1) lower serum levels of AST, ALT, creatinine, and urea; (2) lower levels of the lipid peroxide MDA; and (3) higher activities of the antioxidant enzymes CAT and GPx.

Conclusion

Cotreatment with tamoxifen, hesperidin, and camel milk exosomes synergistically inhibited MCF7 proliferation, migration and minimized tamoxifen adverse effects. Therefore, exosomes and hesperidin could be utilized as safe adjuvants/vehicles to tamoxifen during breast cancer chemotherapy.

中文翻译：

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骆驼乳外泌体、他莫昔芬和橙皮苷联合治疗对乳腺癌的影响

背景

使用标准化疗药物他莫昔芬 (Tam)、天然产物橙皮苷 (Hes) 或骆驼奶外泌体 (Exo) 进行个体治疗已被证明可抑制乳腺癌 MCF7 细胞增殖。然而，关于它们在体外和体内对 MCF7 的综合影响知之甚少。

目标

本研究旨在探讨 Tam、Hes 和 Exo 的联合治疗是否可以在体外和体内协同抑制 MCF7 的增殖并减少 Tam 的副作用。

结果

与单独治疗相比，Tam、Hes 和 Exo 的联合治疗显着抑制了 MCF7 增殖。与单独治疗相比，这种联合治疗还对 MCF7 具有更高的凋亡、抗迁移和抗侵袭作用，如以下所示；(1) Bax和 caspase3 上调和Bcl2下调；（2）乳腺癌相关基因（EGFR和ERα）的下调；(3) MMP9的下调和TIMP1的上调; (4) 迁移细胞数量减少（transwell 试验）。体内研究（MCF7 异种移植物诱导的乳腺癌小鼠模型）的结果证实了这种治疗潜力。共同治疗的小鼠在异种移植物中具有最小的肿瘤大小、最高的Bax和 caspase3、最低的Bcl2和VEGF表达。这种协同治疗更安全，并减少了 Tam 的副作用，如下所示：(1) 降低血清 AST、ALT、肌酐和尿素水平；(2) 脂质过氧化物 MDA 水平较低；(3) 抗氧化酶CAT和GPx的活性更高。

结论

用他莫昔芬、橙皮苷和骆驼奶外泌体共同处理可协同抑制 MCF7 增殖、迁移，并将他莫昔芬的不良反应降至最低。因此，外泌体和橙皮苷可作为乳腺癌化疗期间他莫昔芬的安全佐剂/载体。