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目的研究姜黄素衍生物mPEG2k-Gly-Cur,mPEG2k-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,mPEG2k-Gly-Cur和mPEG2k-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。
Objective To study the in vitro release of curcumin derivatives mPEG2k-Gly-Cur, mPEG2k-Gly-Cur-OA and Cur-OA2 and their anti-tumor effects in vitro. Methods High performance liquid chromatography (HPLC) was used to study the hydrolysis and release characteristics of curcumin derivatives in the culture supernatant of human hepatocellular carcinoma cell line HepG2. The anti-tumor activity of curcumin derivatives in vitro was evaluated by MTT assay. Results The HPLC conditions of curcumin were established. In inactivated cell culture supernatants, mPEG2k-Gly-Cur and mPEG2k-Gly-Cur-OA could release curcumin slowly at a relatively suitable speed, while Cur-OA2 release Very slow; however, the release rate of curcumin derivatives in non-inactivated cell culture supernatant was significantly accelerated, indicating that the derivatives can be accelerated release by enzymatic reaction. In vitro MTT experiments confirmed that three curcumin derivatives have better anti-tumor effect, and Cur-OA2 activity strongest, but the relative free curcumin decreased. Conclusion The derivatization of curcumin phenolic hydroxyl group can effectively improve the stability in aqueous solution. However, oleic acid di-esterified derivatives may enhance the efficacy of phagocytosis of hepatoma cells, which deserves further systematic study.