Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
Biomed Pharmacother. 2024 Nov;180:117429. doi: 10.1016/j.biopha.2024.117429. Epub 2024 Sep 17.
Orlistat (Orli) is an anti-obesity medication that has been approved by the US Food and Drug Administration. It has relatively limited oral bioavailability with promising inhibitory effects on cell proliferation as well as reducing the growth of tumors.
This investigation was done to evaluate the potential protective effect of Tamoxifen/Orlistat nanocrystals alone or in combination against Solid Ehrlich Carcinoma (SEC) and to clarify the possible underlying influences.
The liquid antisolvent precipitation technique (bottom-up technology) was utilized to manufacture Orlistat Nanocrystals. To explore potential causes for the anti-tumor action, female Swiss Albino mice bearing SEC were randomly assigned into five equal groups (n = 6). Group 1: Tumor control group, group 2: Tam group: tamoxifen (0.01 g/kg, IP), group 3: Free-Orli group: orlistat (0.24 g/kg, IP), group 4: Nano-Orli: orlistat nanocrystals (0.24 g/kg, IP), group 5: Tam-Nano-Orli: Both doses of Tam and Nano-Orli. All treatments were administered for 16 days.
The untreated mice showed development in the tumor volume and weight. As well as histopathology results from these mice revealed many tumor large cells as well as solid sheets of malignant cells. Also, untreated mice showed raised VEGF and TGF-1beta content. Moreover, results of gene expression in the SEC-bearing mice noted upregulation in HIF-1α, MMP-9, Bcl-2, and P27 gene expression and downregulation of TXNIP, BAX, and P53 gene expression. On the other hand, administrated TAM, Free-Orli, Nano-Orli, and a combination of Tam-Nano-Orli distinctly suppressed the tumor effects on estimated parameters with special reference to Tam-Nano-Orli.
The developed Tamoxifen/Orlistat nanocrystals combination could be considered a promising approach to augment antitumor effects.
奥利司他（Orli）是一种已获得美国食品和药物管理局批准的抗肥胖药物。它的口服生物利用度相对有限，但具有有希望的细胞增殖抑制作用，并能减少肿瘤生长。
本研究旨在评估单独使用或联合使用他莫昔芬/奥利司他纳米晶体对固体艾氏腹水癌（SEC）的潜在保护作用，并阐明可能的潜在影响。
利用液相抗溶剂沉淀技术（自上而下技术）制备奥利司他纳米晶体。为了探讨抗肿瘤作用的潜在原因，将患有 SEC 的雌性瑞士白化病小鼠随机分为五组（每组 n = 6）。第 1 组：肿瘤对照组；第 2 组：Tam 组：他莫昔芬（0.01 g/kg，IP）；第 3 组：游离-Orli 组：奥利司他（0.24 g/kg，IP）；第 4 组：Nano-Orli：奥利司他纳米晶体（0.24 g/kg，IP）；第 5 组：Tam-Nano-Orli：给予两种剂量的 Tam 和 Nano-Orli。所有治疗均进行 16 天。
未经处理的小鼠肿瘤体积和重量均有增长。这些小鼠的组织病理学结果显示，许多肿瘤细胞较大，且有大量恶性细胞成片生长。此外，未经处理的小鼠显示出 VEGF 和 TGF-β1 含量升高。此外，SEC 荷瘤小鼠的基因表达结果显示，HIF-1α、MMP-9、Bcl-2 和 P27 基因表达上调，而 TXNIP、BAX 和 P53 基因表达下调。另一方面，给予 TAM、游离-Orli、Nano-Orli 以及 Tam-Nano-Orli 联合治疗明显抑制了肿瘤对估计参数的影响，尤其是 Tam-Nano-Orli 联合治疗。
开发的他莫昔芬/奥利司他纳米晶体联合治疗可能被认为是增强抗肿瘤作用的一种有前途的方法。
