背景:乳腺癌是全球女性死亡的主要原因。用于治疗癌症的抗肿瘤剂或疗法可以延长寿命,但随后观察到由于产生的广泛副作用而使生活质量恶化。雪莲是喜马拉雅山的潜在药用植物,具有明显的民族药理特性。雪莲属植物中存在的植物化学物质具有抗癌潜力,并保证雪莲属植物无副作用或副作用最小,并旨在将该植物用作预防或治疗癌症的候选药物。
目的:本研究旨在评估雪莲根提取物(SL)在大鼠乳腺肿瘤模型中的抗肿瘤活性。
方法:通过血清生化(ALT,AST,ALP,总蛋白质,肌酐和BUN),氧化应激参数(脂质过氧化,过氧化氢酶和还原型谷胱甘肽),促炎细胞因子(TNF-α和NF-κB),免疫组织化学标记(Ki-67,MMP-9和VEGF),实时PCR(PCNA,p53,bax,bcl-2和caspase-3,基因)和分子对接。
结果:抑制肿瘤参数,肝脏变化最小(ALT,AST和ALP)和肾脏酶(肌酐和BUN),MDA活性降低,GSH和过氧化氢酶水平升高,降低促炎细胞因子水平,即TNF-α和NF-κB,减少总体和组织形态学变化,体内大鼠模型中Ki-67、MMP-9和VEGF的表达下降,与癌症相关基因的mRNA表达以及脱氢莫司内酯和谷草内酯与NF-κB和TNF-α的对接证明了SL根提取物的化学预防作用。
结论:体内试验阐明了通过降低生化指标证明的雪莲根提取物的抗肿瘤活性,氧化应激参数,组织学变化,促炎细胞因子(NF-κB和TNF-α),细胞增殖(Ki-67),在500mg/kg体重的剂量下,SL提取物具有最高抗肿瘤作用的转移(MMP-9)和新生血管形成(VEGF)标志物。因此,本研究表明需要使用根提取物雪莲中存在的活性成分作为治疗乳腺癌的治疗方案。
BACKGROUND: Breast cancer is a major cause of death among human females across the globe. The anti-neoplastic agents or therapies used for the treatment of cancers can enhance longevity but are subsequently observed to deteriorate the quality of life due to the extensive side effects produced. Saussurea costus is a potential medicinal plant of the Himalayas with noticeable ethnopharmacological properties. The phytochemicals present in Saussurea costus are responsible for anti-carcinogenic potential and warranted nil or minimal side effects of Saussurea costus and directed to use this plant as a preventive or therapeutic drug candidate against cancers.
OBJECTIVE: The present study was planned to evaluate the anti-neoplastic activity of Saussurea costus root extract (SL) in rat mammary tumour model.
METHODS: The anti-neoplastic activity of SL root extract at 3 different doses (100, 250 and 500 mg/kg BW) for 18 weeks against 12-dimethylbenz (a) anthracene (DMBA)-induced mammary tumours in Sprague Dawley (SD) female rats was analyzed through serum biochemistry (ALT, AST, ALP, Total protein, Creatinine and BUN), oxidative stress parameters (Lipid peroxidation, Catalase and Reduced glutathione), pro-inflammatory cytokines (TNF-α and NF-κB), immunohistochemical markers (Ki-67, MMP-9 and VEGF), real-time PCR (PCNA, p53, bax, bcl-2 and caspase-3, genes) and molecular docking.
RESULTS: Inhibition of tumour parameters, minimal alteration in the liver (ALT, AST and ALP) and kidney enzymes (Creatinine and BUN), decreased activity of MDA, elevated levels of GSH and catalase, reduction in the levels of pro-inflammatory cytokines i.e. TNF-α and NF-κB, reduced gross and histomorphological changes, declined expression of Ki-67, MMP-9 and VEGF in vivo rat model, mRNA expression of cancer-related genes and docking of dehydrocostus lactone and costunolide with NF-κB and TNF-α demonstrated the chemopreventive action of SL root extract.
CONCLUSIONS: The in-vivo trial elucidates anti-neoplastic activity of Saussurea costus root extract as demonstrated through the reduction of biochemical indices, oxidative stress parameters, histological changes, pro-inflammatory cytokines (NF-κB and TNF-α), cellular proliferation (Ki-67), metastases (MMP-9) and neovascularization (VEGF) markers with highest anti-neoplastic effect of SL extract at the dose of 500 mg/kg body weight. Therefore, the present study signifies the need to use the active principles present in the root extract of Saussurea costus against breast cancer as a therapeutic regimen.