Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma

Lipids in Health and Disease

Zhen Liu²  Rui-Yan Li²  Qing-Yu Wang²  Bo-Yan Zhang³  Chen-Yu Wang³  Lan-Yu Zhu¹  Yan-Guo Qin² 

[1] Nursing School, Changchun University of Chinese Medicine, Changchun 130117, Jilin, China;Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, Jilin, China;Norman Bethune Medical School, Jilin University, Changchun 130021, Jilin, China

关键词: Glycol chitosan;    Inhibition;    Migration;    Membrane potential;    Osteosarcoma;   

Others  :  1220957
DOI  :  10.1186/s12944-015-0068-4

 received in 2015-02-23, accepted in 2015-06-26,  发布年份 2015

【 摘 要 】

Background

Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis.

Methods

The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied.

Results

MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC ₅₀of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice.

Conclusions

Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma.

【 授权许可】

   
2015 Qin et al.

【 图 表 】

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