Aims

Doxorubicin (Dox) is routinely used for breast cancer treatment but toxicity and drug resistance limit its use. The objective of the study was to investigate the protective effects of hesperidin alone and in combination with doxorubicin against experimentally induced breast cancer in female rats.

Methods

Breast cancer (BC) was induced by administration of 7,12-dimethylbenz(a)anthracene (DMBA) through subcutaneous injection into the 3rd right mammary gland of female Wistar rats. Hesperidin (Hes) pretreated groups were started with Hes (200 mg/kg) two weeks prior to DMBA induction. Animals were randomly divided into nine groups namely vehicle control, DMBA-induced, Dox 4 mg/kg, Dox 2 mg/kg, Hes (200 mg/kg), Hes (200 mg/kg) plus Dox 4 mg/kg treated groups and Hes pretreated groups treated with DMBA, Dox 4 mg/kg and Dox 2 mg/kg.

Key findings

Hes pretreated groups showed reduced tumor occurrence, tumor volume and increased survival rate as compared to DMBA-induced group of animals. Hes pretreated animals treated with Dox 4 mg/kg and 2 mg/kg exhibited significant reduction in malondialdehyde and improvement in levels of glutathione and inflammatory markers like IL-6, TNF-α, NF-κB, IFN-γ as compared to Dox 4 mg/kg and 2 mg/kg treated animals. Histopathology and Ki67 expression depicted better control of tumor with Hes pretreatment groups as compared to DMBA-induced. Histopathology of vital organs of Hes pretreated groups treated with Dox revealed lesser toxicity than Dox treated groups.

Significance

Hesperidin possesses protective effect against experimentally induced breast cancer in female rats that appears to be related to attenuation of Ki67 expression.

中文翻译：

---

橙皮苷通过减弱 Ki67 表达对雌性大鼠 DMBA 诱导的乳腺癌的保护作用

宗旨

多柔比星 (Dox) 常用于乳腺癌治疗，但毒性和耐药性限制了其使用。该研究的目的是研究橙皮苷单独和与阿霉素联合对雌性大鼠实验诱导的乳腺癌的保护作用。

方法

乳腺癌 (BC) 是通过将 7,12-二甲基苯并 ( a ) 蒽 (DMBA) 皮下注射到雌性 Wistar 大鼠的右侧第 3 乳腺而诱发的。橙皮苷 (Hes) 预处理组在 DMBA 诱导前两周开始使用 Hes (200 mg/kg)。将动物随机分为九组，即溶媒对照、DMBA 诱导、Dox 4 mg/kg、Dox 2 mg/kg、Hes (200 mg/kg)、Hes (200 mg/kg) 加 Dox 4 mg/kg 治疗组用DMBA、Dox 4 mg/kg和Dox 2 mg/kg处理的Hes预处理组。

主要发现

与 DMBA 诱导的动物组相比，Hes 预处理组显示出减少的肿瘤发生率、肿瘤体积和增加的存活率。与 Dox 4 相比，用 Dox 4 mg/kg 和 2 mg/kg 处理的 Hes 预处理动物表现出丙二醛的显着减少和谷胱甘肽和炎症标志物（如 IL-6、TNF-α、NF-κB、IFN-γ 水平的改善） mg/kg 和 2 mg/kg 处理的动物。组织病理学和 Ki67 表达表明，与 DMBA 诱导的相比，Hes 预处理组对肿瘤的控制更好。用 Dox 处理的 Hes 预处理组的重要器官的组织病理学显示比 Dox 处理组的毒性更小。

意义

橙皮苷对雌性大鼠实验诱导的乳腺癌具有保护作用，这似乎与 Ki67 表达的减弱有关。