姜黄素衍生物体外释放及抗肿瘤作用研究

Study on Release and Anti-tumor Effect of Curcumin Derivatives in Vitro

关键词:  姜黄素衍生物  体外释放  抗肿瘤  聚乙二醇修饰

Key words:  curcumin derivatives  in vitro release  antitumor  PEGylation

摘要:

目的 研究姜黄素衍生物mPEG_2k-Gly-Cur，mPEG_2k-Gly-Cur-OA和Cur-OA₂的体外释放情况及其体外抗肿瘤作用。方法 采用高效液相色谱法，进行姜黄素衍生物在人肝癌细胞株HepG2培养上清液中水解释放特性的研究；采用MTT法对各姜黄素衍生物体外抗肿瘤细胞活性进行初步评价。结果 建立了姜黄素的HPLC检测条件，在灭活的细胞培养上清液中，mPEG_2k-Gly-Cur和mPEG_2k-Gly-Cur-OA可以以相对合适的速度缓慢释放姜黄素，而Cur-OA₂释放非常缓慢；但在未灭活处理的细胞培养上清液中姜黄素衍生物释放速度均明显加快，表明衍生物可以通过酶促反应加速释放。体外MTT实验证实3个姜黄素衍生物具有较好的抗肿瘤作用，而且Cur-OA₂活性最强，但相对游离姜黄素均有所下降。结论 姜黄素酚羟基经衍生化后可有效提高水溶液中稳定性，而油酸双酯化衍生物可能通过肝癌细胞吞噬作用增强药效，值得进一步深入的系统研究。

Abstract:

OBJECTIVE To study the release and anti-tumor effect of curcumin derivatives, mPEG_2k-Gly-Cur, mPEG_2k-Gly-Cur-OA and Cur-OA₂，in vitro. METHODS The release property of curcumin derivatives in HepG2 cell culture supernatant was studied by HPLC method; furthermore, the antitumor activity of the derivatives in vitro was evaluated by MTT method with HepG2 cell lines. RESULTS HPLC detection conditions of curcumin were established. In deactivated cell culture supernatant, mPEG_2k-Gly-Cur and mPEG_2k-Gly-Cur-OA could release curcumin in a rational speed, while the release speed of Cur-OA₂ was too slow to be able to show any potential application, however, the release rate of curcumin from Cur-OA₂ and other curcumin derivatives was remarkably promoted in the untreated HepG2 cell culture supernatant, which may imply enzyme hydrolysis takes place. Additionally, MTT assay confirmed that three derivatives still had cell growth inhibition activity against HepG2 cell lines, and the derivative Cur-OA₂ with the strongest activity, but all were less efficient than curcumin. CONCLUSION Curcumin stability can be effectively improved after modification and the oleic acid double esterification derivative may enhance anti-hepatic carcinoma activity by cell phagocytize way, which deserves further research.