Maleklou Nargess, Allameh Abdolamir, Kazemi Bahram
Medical Physics and Biomedical Engineering Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
In Vitro Cell Dev Biol Anim. 2016 Dec;52(10):989-1000. doi: 10.1007/s11626-016-0072-7. Epub 2016 Aug 8.
In recent years, targeted delivery systems have been used along with combinatorial therapy to decrease drug resistance and increase cancer therapy efficacy. The anti-proliferative effects of vitamin D3 (VD3) on cancerous cells, such as C6 glioma, with active hedgehog pathways raised the question as to whether pre-targeting C6 glioma cells with VD3-loaded nanoparticles (VD3NPs) can enhance the anti-tumor effects of doxorubicin, epirobicin, and docetaxel on this drug-resistant cell line. Here, studying at cellular, nuclear, protein, and gene levels we demonstrated that VD3NP-doxorubicin and VD3NP-epirobicin combinations increased the probability of chemotherapy/radiotherapy resistance and cancer stem cell (CSC) properties in C6 glioma significantly (P < 0.05), compared to doxorubicin and epirobicin alone. However, VD3NP-docetaxel combination may have the potential in sensitizing C6 cells to ionizing irradiation, but this combination also increased the CSC properties and the probability of drug resistance significantly (P < 0.05), compared to docetaxel alone. Although our previous study showed that targeted delivery of VD3 reduced the rate of proliferation significantly (P < 0.05) in C6 glioma cells (a drug-resistant cell line), here we concluded that combinatorial therapy of exogenous VD3 with doxorubicin, epirobicin, and docetaxel not only did not lead to the enhancement of cytotoxic effects of the aforementioned drugs but also increased the cancerous characteristics in C6 glioma, in vitro.
近年来，靶向递送系统已与联合疗法一起使用，以降低耐药性并提高癌症治疗效果。维生素D3（VD3）对具有活跃刺猬通路的癌细胞（如C6胶质瘤）的抗增殖作用引发了一个问题，即预先用负载VD3的纳米颗粒（VD3NPs）靶向C6胶质瘤细胞是否能增强阿霉素、表柔比星和多西他赛对这种耐药细胞系的抗肿瘤作用。在这里，我们在细胞、细胞核、蛋白质和基因水平上进行研究，结果表明，与单独使用阿霉素和表柔比星相比，VD3NP-阿霉素和VD3NP-表柔比星联合用药显著增加了C6胶质瘤化疗/放疗耐药性和癌症干细胞（CSC）特性的概率（P < 0.05）。然而，与单独使用多西他赛相比，VD3NP-多西他赛联合用药可能具有使C6细胞对电离辐射敏感的潜力，但这种联合用药也显著增加了CSC特性和耐药概率（P < 0.05）。尽管我们之前的研究表明，VD3的靶向递送显著降低了C6胶质瘤细胞（一种耐药细胞系）的增殖率（P < 0.05），但在这里我们得出结论，外源性VD3与阿霉素、表柔比星和多西他赛的联合疗法不仅没有增强上述药物的细胞毒性作用，反而在体外增加了C6胶质瘤的癌性特征。
