Hu Ying-Jie, Zhang Jing-Ying, Luo Qian, Xu Jia-Rui, Yan Yan, Mu Li-Min, Bai Jing, Lu Wan-Liang
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Nanomaterials (Basel). 2018 Oct 9;8(10):804. doi: 10.3390/nano8100804.
The heterogeneity of breast cancer and the development of drug resistance are the relapse reasons of disease after chemotherapy. To address this issue, a combined therapeutic strategy was developed by building the nanostructured dihydroartemisinin plus epirubicin liposomes. Investigations were performed on human breast cancer cells in vitro and xenografts in nude mice. The results indicated that dihydroartemisinin could significantly enhance the efficacy of epirubicin in killing different breast cancer cells in vitro and in vivo. We found that the combined use of dihydroartemisinin with epirubicin could efficiently inhibit the activity of Bcl-2, facilitate release of Beclin 1, and further activate Bax. Besides, Bax activated apoptosis which led to the type I programmed death of breast cancer cells while Beclin 1 initiated the excessive autophagy that resulted in the type II programmed death of breast cancer cells. In addition, the nanostructured dihydroartemisinin plus epirubicin liposomes prolonged circulation of drugs, and were beneficial for simultaneously delivering drugs into breast cancer tissues. Hence, the nanostructured dihydroartemisinin plus epirubicin liposomes could provide a new therapeutic strategy for treatment of breast cancer.
乳腺癌的异质性和耐药性的产生是化疗后疾病复发的原因。为了解决这个问题，通过构建纳米结构的双氢青蒿素加表柔比星脂质体开发了一种联合治疗策略。对人乳腺癌细胞进行了体外研究，并在裸鼠体内进行了异种移植研究。结果表明，双氢青蒿素在体外和体内均可显著提高表柔比星对不同乳腺癌细胞的杀伤效果。我们发现，双氢青蒿素与表柔比星联合使用可有效抑制Bcl-2的活性，促进Beclin 1的释放，并进一步激活Bax。此外，Bax激活凋亡导致乳腺癌细胞的I型程序性死亡，而Beclin 1引发过度自噬导致乳腺癌细胞的II型程序性死亡。此外，纳米结构的双氢青蒿素加表柔比星脂质体延长了药物的循环时间，有利于将药物同时递送至乳腺癌组织。因此，纳米结构的双氢青蒿素加表柔比星脂质体可为乳腺癌治疗提供一种新的治疗策略。
