Elaidy Samah M, El-Kherbetawy Mohamed K, Abed Sally Y, Alattar Abdullah, Alshaman Reem, Eladl Mohamed Ahmed, Alamri Eman Saad, Al Balawi Aisha Nawaf, Zaid AbdelNaser, Elkazzaz Amany Y, Abdelkhalig Sozan M, Hamed Ziad E, Zaitone Sawsan A
Clinical Pharmacology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Pharmaceuticals (Basel). 2023 Mar 7;16(3):405. doi: 10.3390/ph16030405.
Stromal cell-derived factor-1 (SDF1) and its C-X-C chemokine receptor type 4 receptor (CXCR4) are significant mediators for cancer cells' proliferation, and we studied their expression in Ehrlich solid tumors (ESTs) grown in mice. α-Hederin is a pentacyclic triterpenoid saponin found in Hedera or Nigella species with biological activity that involves suppression of growth of breast cancer cell lines. The aim of this study was to explore the chemopreventive activity of α-hederin with/without cisplatin; this was achieved by measuring the reduction in tumor masses and the downregulation in SDF1/CXCR4/pAKT signaling proteins and nuclear factor kappa B (NFκB). Ehrlich carcinoma cells were injected in four groups of Swiss albino female mice (Group1: EST control group, Group2: EST + α-hederin group, Group3: EST + cisplatin group, and Group4: EST+α-hederin/cisplatin treated group). Tumors were dissected and weighed, one EST was processed for histopathological staining with hematoxylin and eosin (HE), and the second MC was frozen and processed for estimation of signaling proteins. Computational analysis for these target proteins interactions showed direct-ordered interactions. The dissected solid tumors revealed decreases in tumor masses (21%) and diminished viable tumor regions with significant necrotic surrounds, particularly with the combination regimens. Immunohistochemistry showed reductions (50%) in intratumoral NFκβ in the mouse group that received the combination therapy. The combination treatment lowered the SDF1/CXCR4/-AKT proteins in ESTs compared to the control. In conclusion, α-hederin augmented the chemotherapeutic potential of cisplatin against ESTs; this effect was at least partly mediated through suppressing the chemokine SDF1/CXCR4/-AKT/NFκB signaling. Further studies are recommended to verify the chemotherapeutic potential of α-hederin in other breast cancer models.
基质细胞衍生因子-1（SDF1）及其C-X-C趋化因子受体4型受体（CXCR4）是癌细胞增殖的重要介质，我们研究了它们在小鼠体内生长的艾氏实体瘤（ESTs）中的表达。α-常春藤皂苷是一种在常春藤或黑种草属植物中发现的五环三萜皂苷，具有抑制乳腺癌细胞系生长的生物活性。本研究的目的是探讨α-常春藤皂苷联合或不联合顺铂的化学预防活性；这是通过测量肿瘤肿块的减少以及SDF1/CXCR4/pAKT信号蛋白和核因子κB（NFκB）的下调来实现的。将艾氏癌细胞注射到四组瑞士白化雌性小鼠中（第1组：EST对照组，第2组：EST + α-常春藤皂苷组，第3组：EST + 顺铂组，第4组：EST+α-常春藤皂苷/顺铂治疗组）。解剖肿瘤并称重，一个EST用于苏木精和伊红（HE）组织病理学染色，第二个MC冷冻并用于信号蛋白的评估。对这些靶蛋白相互作用的计算分析显示了直接有序的相互作用。解剖的实体瘤显示肿瘤肿块减少（约21%），存活肿瘤区域减少，周围有明显坏死，特别是联合治疗方案。免疫组织化学显示，接受联合治疗的小鼠组肿瘤内NFκβ减少（约50%）。与对照组相比，联合治疗降低了ESTs中的SDF1/CXCR4/-AKT蛋白。总之，α-常春藤皂苷增强了顺铂对ESTs的化疗潜力；这种作用至少部分是通过抑制趋化因子SDF1/CXCR4/-AKT/NFκB信号传导介导的。建议进一步研究以验证α-常春藤皂苷在其他乳腺癌模型中的化疗潜力。
