El-Masry Thanaa A, El-Nagar Maysa M F, El Mahdy Nageh A, Alherz Fatemah A, Taher Reham, Osman Enass Y
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Pharmaceuticals (Basel). 2024 Apr 19;17(4):527. doi: 10.3390/ph17040527.
An FDA-approved kinase inhibitor called sorafenib (SOR) is used to treat primary kidney and liver cancer as well as to stop the spread of advanced breast cancer. Side effects from SOR, such as palmar-plantar erythrodysesthesia syndrome, can negatively impact an individual's quality of life. There are a lot of data supporting the importance of lycopene (LYC) in preventing cancer. The antitumor properties of the combination of sorafenib and lycopene were examined in this study. A viability test against MDA-MB-231 was used to assess the anticancer efficacy of sorafenib, lycopene, and their combination in vitro. Moreover, a cell cycle analysis and Annexin-V/PI double staining were performed by using flow cytometry. In addition, the protein level of JNK-1, ERK-1, Beclin-1, P38, and P53 of the MDA-MB-231 cell line was estimated using ELISA kits. In addition, mice with SEC were divided into four equal groups at random ( = 10) to investigate the possible processes underlying the in vivo antitumor effect. Group IV (SEC-SOR-LYC) received SOR (30 mg/kg/day, p.o.) and LYC (20 mg/kg/day, p.o.); Group I received the SEC control; Group II received SEC-SOR (30 mg/kg/day, p.o.); and Group III received SEC-LYC (20 mg/kg/day, p.o.). The findings demonstrated that the combination of sorafenib and lycopene was superior to sorafenib and lycopene alone in causing early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis and autophagy. Likewise, the combination of sorafenib and lycopene demonstrated inhibition of the levels of Bcl-2, Ki-67, VEGF, IL-1β, and TNF-α protein. Otherwise, the quantities of the proteins BAX, P53, and caspase 3 were amplified. Furthermore, the combined treatment led to a substantial increase in , , and gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor's decreased weight and volume, hence demonstrating its potential anticancer effect.
一种名为索拉非尼（SOR）的经美国食品药品监督管理局（FDA）批准的激酶抑制剂，被用于治疗原发性肾癌和肝癌，以及阻止晚期乳腺癌的扩散。索拉非尼的副作用，如手足红斑感觉异常综合征，会对个人生活质量产生负面影响。有大量数据支持番茄红素（LYC）在预防癌症方面的重要性。本研究考察了索拉非尼与番茄红素联合使用的抗肿瘤特性。采用针对MDA - MB - 231细胞的活力测试来评估索拉非尼、番茄红素及其组合在体外的抗癌效果。此外，利用流式细胞术进行细胞周期分析和膜联蛋白V/碘化丙啶（Annexin-V/PI）双染。另外，使用酶联免疫吸附测定（ELISA）试剂盒评估MDA - MB - 231细胞系中JNK - 1、ERK - 1、Beclin - 1、P38和P53的蛋白水平。此外，将患有实体瘤（SEC）的小鼠随机分为四个相等的组（每组n = 10），以研究体内抗肿瘤作用的潜在机制。第四组（SEC - SOR - LYC）接受索拉非尼（30毫克/千克/天，口服）和番茄红素（20毫克/千克/天，口服）；第一组接受SEC对照；第二组接受SEC - SOR（30毫克/千克/天，口服）；第三组接受SEC - LYC（20毫克/千克/天，口服）。研究结果表明，索拉非尼与番茄红素联合使用在导致早期细胞周期停滞、抑制癌细胞活力、增加细胞凋亡和自噬方面优于单独使用索拉非尼和番茄红素。同样，索拉非尼与番茄红素联合使用显示出对Bcl - 2、Ki - 67、血管内皮生长因子（VEGF）、白细胞介素 - 1β（IL - 1β）和肿瘤坏死因子 - α（TNF - α）蛋白水平的抑制作用。此外，促凋亡蛋白（BAX）、P53和半胱天冬酶3的量增加。此外，与等效剂量的单一疗法相比，联合治疗导致 、 和 基因表达显著增加。索拉非尼与番茄红素联合使用增强了细胞凋亡并减轻了炎症，这从肿瘤重量和体积的减小可以看出，因此证明了其潜在的抗癌作用。 （注：原文中“ 、 和 ”处有信息缺失未明确指出具体基因名称）
