乳腺癌被认为是女性普遍的公共卫生困境。由于传统抗癌疗法的高毒性和低选择性,在癌症预防和治疗中使用植物衍生的天然产物的趋势正在增长。阿什瓦甘达(Withaniasomnifera,WS)已在地中海地区和阿育吠陀医学中使用了数千年,作为功能性食品和具有抗癌活性的药用植物。此外,间歇性禁食(IF)最近已被用于癌症治疗。因此,WS和IF联合化疗为治疗癌症和降低化疗耐药提供了可能的解决方案.在这项研究中,WS根(WSR),如果,和顺铂在顺铂敏感(EMT6/P)和顺铂耐药(EMT6/CPR)小鼠乳腺细胞系中进行了测试。使用液相色谱-质谱(LC-MS)分析来分析WSR提取物的植物化学物质含量。对WSR提取物的抗增殖和凋亡作用进行了评估,顺铂,以及使用[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴化物](MTT)和caspase-3测定法进行体外组合。一项体内研究用于评估WSR提取物的效果,如果,顺铂,以及它们在小鼠中的组合被灌输EMT6/P和EMT6/CPR细胞。还使用肝酶和肌酐测定研究了安全性。体外,WSR提取物和顺铂在两种细胞系中均具有协同作用。相同的组合在两种细胞系中诱导的凋亡效应高于单一处理。在体内,WSR提取物的几种组合,如果,在植入EMT6/P和EMT6/CPR细胞系的小鼠中,或顺铂导致肿瘤大小显著减小,并提高治愈率。IF处理组显示出血清葡萄糖的显着降低和β-羟基丁酸酯(BHB)水平的升高。在安全档案中,WSR提取物,如果,他们的组合是安全的.总的来说,除了顺铂之外,WSR提取物和IF的组合通过诱导细胞凋亡来减少癌细胞的增殖,为乳腺癌治疗提供了有希望的解决方案。此外,他们减少顺铂对肝脏和肾脏的毒性。
Breast cancer is considered a universal public health dilemma in women. Due to the high toxicity and low selectivity of conventional anticancer therapies, there is a growing trend of using plant-derived natural products in cancer prevention and therapy. Ashwagandha (Withania somnifera, WS) has been used in the Mediterranean region and Ayurvedic medicine for millennia as a functional food and a medicinal plant with anticancer activity. Besides, intermittent fasting (IF) has been engaged recently in cancer treatment. Hence, the combination of WS and IF provides possible solutions to treat cancer and reduce chemoresistance when combined with chemotherapy. In this
study, WS root (WSR), IF, and cisplatin were tested on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. The phytochemical content of the WSR extract was analyzed using liquid chromatography-mass spectrometry (LC-MS) analysis. Antiproliferative and apoptotic effects were assessed for WSR extract, cisplatin, and their combination in vitro using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) and caspase-3 assays. An in vivo
study was used to assess the effect of WSR extract, IF, cisplatin, and their combinations in mice inculcated with EMT6/P and EMT6/CPR cells. The safety profile was also investigated using liver enzymes and creatinine assays. In vitro, WSR extract and cisplatin had a synergistic effect in both cell lines. The same combination induced an apoptotic effect higher than the single treatment in both cell lines. In vivo, several combinations of WSR extract, IF, or cisplatin caused significant tumor size reduction and improved the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. IF-treated groups showed a significant reduction in serum glucose and an elevation in β-hydroxybutyrate (BHB) levels. In the safety profile, WSR extract, IF, and their combinations were safe. Overall, the combination of WSR extract and IF provides a promising solution for breast cancer treatment besides cisplatin by reducing the proliferation of cancer cells through induction of apoptosis. Moreover, they minimize cisplatin toxicity to the liver and kidney.