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首页> 外文期刊>Journal of biomedical science. >Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES
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Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

机译：紫草素通过诱导RANTES增强基于基因的癌症疫苗的功效

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BackgroundShikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs), a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation.MethodThe mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100) DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100) tumor model.ResultsAmong various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells.ConclusionTogether, our findings suggest that shikonin can effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site.
机译：背景技术紫草素是一种从紫草紫苏中提取的植物化学物质，已被证明具有多种药理活性，包括促进肉芽肿形成，伤口愈合，抗炎和其他作用，并在本研究中探索了用于疫苗接种的免疫调节剂活性。基于透皮基因的疫苗是一种将编码特定肿瘤抗原的DNA转基因递送至宿主皮肤组织的有吸引力的方法。皮肤树突状细胞（DCs）是一种有效的抗原呈递细胞类型，已知在传递和协调针对癌症的肿瘤抗原特异性免疫中起关键作用。方法采用RT-PCR和ELISA法分别检测RANTES的mRNA和蛋白表达。通过免疫组织化学分析评估了RANTES的区域表达和测试皮肤中的组织损伤。进行了异硫氰酸荧光素敏化试验，以追踪DC从皮肤疫苗接种部位到引流淋巴结的运输。在人gp100转染的B16（B16 / hgp100）肿瘤模型中研究了紫草素对基因枪传递的人gp100（hgp100）DNA癌症疫苗的佐剂作用。结果在测试的各种植物化学物质中，紫草素诱导正常人RANTES的最高表达皮肤组织。相比之下，小鼠RANTES cDNA基因转染可在更长的时间内诱导更高水平的mRANTES表达，但会造成更大范围的皮肤损伤。在基因枪介导的疫苗接种之前，将紫草素局部应用到免疫部位可以增加皮肤DC迁移到引流淋巴结的数量。在B16 / hgp100肿瘤模型中以紫草素预处理作为佐剂的hgp100 cDNA基因疫苗接种方案可增加靶肿瘤细胞上脾细胞和淋巴结细胞的细胞毒性T淋巴细胞活性。通过在皮肤免疫部位诱导RANTES表达来开发基于基因的癌症疫苗。

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