阿霉素是产生自由基诱导毒性的化疗药物。天然试剂用于增强或改善化疗的毒性。研究抗氧化剂或促氧化剂是否应与化疗一起使用的研究都没有在同一项研究中解决它们的功效。因此,这项研究的目的是研究阿霉素与两种很少在体内研究的天然抗癌剂之间的潜在协同作用;艾利希肿瘤小鼠模型中的抗氧化剂“山奈酚”和促氧化剂“吡哌酮胺”。77只白化病小鼠分为11组;肌肉注射Ehrlich腹水癌细胞以发展实体瘤。14天后,肿瘤内注射单一或组合的负载多柔比星的游离或壳聚糖纳米颗粒,胡椒长胺,并进行山奈酚。测量纳米颗粒的肿瘤特征,对肿瘤进行组织病理学检查和通过实时PCR评估癌症相关基因的表达。进行了计算机分子对接以发现Piperlongumine和山奈酚的潜在新靶标。尽管与免费药物相比,接受了总剂量的一半,多柔比星/哌啶多胺-壳聚糖纳米粒联合治疗在减少肿瘤体积方面最有效;下调CyclinD1和BCL2;以及Beclin-1和亲环蛋白A基因调节生长,凋亡,自噬,和转移,分别上调谷胱甘肽过氧化物酶的表达,作为保护免受氧化损伤的防御机制。当与阿霉素联合使用时,山奈酚和胡椒长胺对Ehrlich实体瘤有效。然而,与山奈酚或相同的游离化合物相比,与负载Piperlongumine的壳聚糖纳米颗粒的组合显着增强了其抗癌作用。
Doxorubicin is a chemotherapeutic drug that generates free radical-induced toxicities. Natural agents are used to potentiate or ameliorate the toxicity of chemotherapy. None of the studies investigating whether antioxidants or prooxidants should be used with chemotherapy have addressed their efficacy in the same
study. Therefore, the aim of this
study was to investigate the potential synergy between doxorubicin and two natural rarely in vivo studied anticancer agents; the antioxidant \"Kaempferol\" and prooxidant \"
Piperlongumine\" in Ehrlich tumor mice model. 77 albino mice were divided into 11 groups; Ehrlich ascites carcinoma cells were injected intramuscularly to develop solid tumors. After 14 days, intratumoral injections of single or combinations of free or Chitosan nanoparticles loaded with doxorubicin, Piperlongumine, and Kaempferol were performed. Tumor Characterization of nanoparticles was measured, tumors were histopathologically examined and evaluation of expression for cancer-related genes by real-time PCR. In silico molecular docking was performed to uncover potential novel targets for Piperlongumine and Kaempferol. Despite receiving half of the overall dose compared to the free drugs, the combined doxorubicin/ piperlongumine-chitosan nanoparticles treatment was the most efficient in reducing tumor volume; down-regulating Cyclin D1, and BCL2; as well as the Beclin-1, and Cyclophilin A genes modulating growth, apoptosis, autophagy, and metastasis, respectively; up-regulating the Glutathione peroxidase expression as a defense mechanism protecting from oxidative damage. When combined with doxorubicin, Kaempferol and
Piperlongumine were effective against Ehrlich solid tumors. However, the combination with the
Piperlongumine-loaded chitosan nanoparticles significantly enhanced its anticancer effect compared to the Kaempferol or the same free compounds.