基于光学分子影像技术的吉马酮对乳腺癌抑制活性的在体研究

Traditional Chinese medicine and its main components have certain advantages in prevention and treatment of breast cancer. However, more studies should be taken to support for the clinical application of TCM in cancer remedy. Germacrone is the main constituent of zedoary oil. The present pharmacodynamics studies of germacrone are mainly on the in vitro level. However, the in vivo evaluation of the anti-breast cancer activity of germacrone might provide an important theoretical significance for understanding the activity of germacrone and the clinical usage in future. In this proposal, mesoporous silica nanoparticles modified with 800CW were used to improve the bioavailability of germacrone. The breast cancer cell line MCF-7 was modified with a caspase-3 specific cyclic firefly luciferase reporter gene (pcFluc-DEVD) for establishing the tumor model. Optical molecular imaging techniques were taken to observe the distribution and evaluate the anti-breast cancer activity of germacrone in vivo, following with 3D reconstruction and quantitative analysis of the tumor. Thus, a comprehensive assessment of the breast cancer inhibitory activity of germacrone is accomplished. This proposal could reveal the activity of germacrone in vivo, and established a solid theoretical foundation for developing germacrone as anticancer durgs, while provide an important experimental method system for the studies of anti-breast cancer drugs based on optical molecular imaging.

中药及其主成分在乳腺癌的防治中具有优势，却需要更多的研究来为其临床应用提供支持。目前关于莪术油指标性成分吉马酮的乳腺癌抑制活性研究多停留在离体水平，因此确定吉马酮对乳腺癌的在体作用，无论是为明确吉马酮药效学价值，还是为吉马酮在乳腺癌治疗的临床应用前景都具有重要意义。本项目利用介孔二氧化硅纳米颗粒包封吉马酮，来改善生物利用度；通过在介孔硅表面修饰近红外荧光染料irdye800CW及构建稳定表达caspase-3响应的荧光素酶报告基因乳腺癌细胞系，来建立光学探针体系；采用光学分子影像技术，观测吉马酮在体代谢分布和乳腺癌细胞抑制活性，应用配套的三维重建算法和定量分析方法进行瘤体定位、三维重建及定量计算，描述药物在体疗效的动态过程。从而，完成对吉马酮的乳腺癌抑制活性的在体评估。本项目的完成将在活体实验水平为吉马酮药效研究的提供数据基础，并建立以光学影像技术为基础的乳腺癌治疗药物在体研究方法体系。

中药及其主成分在癌症的防治中具有优势，却需要更多的研究来为其临床应用提供支持。目前关于莪术油指标性成分吉马酮的乳腺癌抑制活性研究多停留在离体水平，因此确定吉马酮对乳腺癌的在体作用，无论是为明确吉马酮药效学价值，还是为吉马酮在乳腺癌治疗的临床应用前景都具有重要意义。本项目采取结构修饰及构建介孔二氧化硅纳米载药体系的方法以求改善吉马酮生物利用度；对吉马酮的乳腺癌细胞抑制活性进行了离体及在体水平的评估；构建了基于光学分子影像技术的天然药物肿瘤抑制活性测试技术平台；并基于构建好的技术平台筛选出两个活性小分子（Britanin及红景天苷）；进一步研究发现Britanin通过调控PI3K/Akt/NF-kappB通路抑制前列腺癌细胞生长；而红景天苷则通过增强机体免疫机制，改善肿瘤微环境来协同阿霉素发挥抑制耐药细胞阿霉素增殖的作用。两个活性小分子的实验完全依托于本项目，是项目构建的实验技术体系的延伸；表明分子影像技术在中药活性成分的研究中具有广阔的应用前景。

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