Targeted delivery of vitamin D3-loaded nanoparticles to C6 glioma cell line increased resistance to doxorubicin, epirubicin, and docetaxel in vitro

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.

Keywords: C6 glioma; Docetaxel; Doxorubicin; Epirubicin; Vitamin D3-loaded nanoparticles.

MeSH terms

  • AC133 Antigen / metabolism
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholecalciferol / pharmacology
  • Cholecalciferol / therapeutic use*
  • DNA / metabolism
  • Docetaxel
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Drug Delivery Systems*
  • Epirubicin / pharmacology
  • Epirubicin / therapeutic use*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • L-Lactate Dehydrogenase / metabolism
  • Nanoparticles / chemistry*
  • Rats
  • Taxoids / pharmacology
  • Taxoids / therapeutic use*


  • AC133 Antigen
  • Taxoids
  • Docetaxel
  • Cholecalciferol
  • Epirubicin
  • Doxorubicin
  • DNA
  • L-Lactate Dehydrogenase