Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31 Vishvigyan Bhawan, M. G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, India.
Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31 Vishvigyan Bhawan, M. G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, India.
Biomed Pharmacother. 2017 May;89:1142-1151. doi: 10.1016/j.biopha.2017.02.110. Epub 2017 Mar 12.
Resveratrol (RSVL) a dietary phytochemical showed to enhance the efficacy of chemotherapeutic drugs. Recently, Salinomycin (SAL) has gained importance as cancer therapeutic value for breast cancer (BC), however, its superfluxious toxicity delimits the utility. Taking the advantage of RSVL, the therapeutic efficacy of RSVL and SAL combination was studied in vitro and in vivo system. Firstly, the synergistic combination dose of RSVL and SAL was calculated and further, the efficacy was examined by wound healing, and Western blots analysis. Further, in vivo study was performed to confirm the effect of colony formation and apoptosis detection by flow cytometry based assays. Further, the molecular mode of action was determined at both transcript and translational level by quantitative Real Time PCR combination in Ehrlich ascitic carcinoma model.The combination of IC20 (R20) of RSVL and IC10 (S10) dose of SAL showed best synergism (CI<1) with ∼5 fold dose advantage of SAL. Gene expression results at mRNA and protein level revealed that the unique combination of RSVL and SAL significantly inhibited epithelial mesenchymal transition (Fibronectin, Vimentin, N-Cadherin, and Slug); chronic inflammation (Cox2, NF-kB, p53), autophagy (Beclin and LC3) and apoptotic (Bax, Bcl-2) markers. Further, i n vivo study showed that low dose of SAL in combination with RSVL increased life span of Ehrlich ascitic mice. Overall, our study revealed that RSVL synergistically potentiated the anticancer potential of SAL against triple negative BC.
白藜芦醇（RSVL）是一种膳食植物化学物质，已被证明能增强化疗药物的疗效。最近，萨利霉素（SAL）作为乳腺癌（BC）的治疗价值引起了人们的重视，但其过多的毒性限制了其应用。利用 RSVL 的优势，我们在体外和体内系统研究了 RSVL 和 SAL 联合治疗的疗效。首先，计算了 RSVL 和 SAL 的协同组合剂量，然后通过伤口愈合和 Western blot 分析进一步检查了疗效。此外，还进行了体内研究，通过流式细胞术检测集落形成和细胞凋亡来证实效果。此外，还通过定量实时 PCR 组合在艾氏腹水癌模型中从转录和翻译水平确定了分子作用模式。RSVL 的 IC20（R20）和 SAL 的 IC10（S10）剂量的组合显示出最佳的协同作用（CI<1），具有约 5 倍的 SAL 剂量优势。mRNA 和蛋白质水平的基因表达结果表明，RSVL 和 SAL 的独特组合显著抑制上皮间质转化（纤连蛋白、波形蛋白、N-钙粘蛋白和 Slug）；慢性炎症（Cox2、NF-kB、p53）、自噬（Beclin 和 LC3）和凋亡（Bax、Bcl-2）标志物。此外，体内研究表明，低剂量 SAL 与 RSVL 联合使用可延长艾氏腹水小鼠的寿命。总的来说，我们的研究表明，RSVL 协同增强了 SAL 对三阴性 BC 的抗癌潜力。
