Han Na-Na, Li Xia, Tao Ling, Zhou Qi
The Fourth Department of Gynaecological Oncology, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi 830001, China.
The Fourth Department of Gynaecological Oncology, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi 830001, China.
Biochem Biophys Res Commun. 2018 Mar 25;498(1):178-185. doi: 10.1016/j.bbrc.2018.01.042. Epub 2018 Jan 6.
Tumor targeting delivery system has been suggested as an attractive strategy against tumor progression. Combination chemotherapy is essential and effective in preventing ovarian cancer. Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is a lipophilic anthraquinone. Emerging evidence indicates that rhein has many pharmacological effects, such as nephroprotective, hepatoprotective, anti-inflammatory, antioxidant, and anticancer activities. In our study, doxorubicin (DOX) and rhein (RHE) co-loaded polymeric micelle (nano-DOX/RHE) were prepared to attenuate drug resistance in ovarian cancer cells while promoting the therapeutic efficiency of DOX. The morphology, particle size (about 25 nm), zeta potential, release profile in vitro, cell proliferation and cytotoxicity effects were calculated. The results suggested that DOX and RHE could be efficiently loaded into micelle nanoparticles, and in vitro study indicated that they could be released from the nanoparticles in an extended period into DOX-resistant SKOV3 cells (SKOV3/DOX). Nano-DOX/RHE exerted an enhanced cytotoxicity and high apoptosis-inducing activities in SKOV3/DOX cells. Importantly, nano-DOX/RHE exhibited better cancer targeting ability, enhancing the anti-tumor efficacy with little toxicity. In conclusion, nano-DOX/RHE promoted the drug target on tumor site with preferable anti-tumor effects, which could be a promising therapeutic strategy against human ovarian cancer.
肿瘤靶向递送系统已被认为是一种对抗肿瘤进展的有吸引力的策略。联合化疗在预防卵巢癌方面至关重要且有效。大黄酸（4,5 - 二羟基蒽醌 - 2 - 羧酸）是一种亲脂性蒽醌。新出现的证据表明，大黄酸具有多种药理作用，如肾保护、肝保护、抗炎、抗氧化和抗癌活性。在我们的研究中，制备了载有阿霉素（DOX）和大黄酸（RHE）的聚合物胶束（纳米DOX/RHE），以减轻卵巢癌细胞的耐药性，同时提高DOX的治疗效果。计算了其形态、粒径（约25nm）、zeta电位、体外释放曲线、细胞增殖和细胞毒性作用。结果表明，DOX和RHE可以有效地负载到胶束纳米颗粒中，体外研究表明它们可以在较长时间内从纳米颗粒释放到耐DOX的SKOV3细胞（SKOV3/DOX）中。纳米DOX/RHE在SKOV3/DOX细胞中表现出增强的细胞毒性和高凋亡诱导活性。重要的是，纳米DOX/RHE表现出更好的癌症靶向能力，在毒性较小的情况下增强了抗肿瘤疗效。总之，纳米DOX/RHE促进了药物在肿瘤部位的靶向作用，具有较好的抗肿瘤效果，这可能是一种有前途的治疗人类卵巢癌的策略。
