Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma
Authors: Bo-Yan Zhang
Lan-Yu Zhu
Chen-Yu Wang
Qing-Yu Wang
Zhen Liu
Yan-Guo Qin
Rui-Yan Li
Journal: Lipids in health and disease (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Osteosarcoma; Retinoic acid chlorochalcone; Glycol chitosan nanoparticle; Cell proliferation; Ezh2 expression
Affiliations: Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China. ., Nursing School, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China. ., Norman Bethune Medical School, Jilin University, Changchun, Jilin, 130021, China. .

Abstract:  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 &lt; 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 IC50 of 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. 

Retracted: Yes

PubPeer comments:
 Brought to my attention by a reader. * Figure 3: Some bands look more similar to each other than expected. ![file] , 
 Figure 4A. * The three panels appear to have been generated from the same groups of cells, except in different combinations. ![file] , 
 Figure 6. * THe MG-63 (top row) and Saos-2 (bottom row) graphs look very similar to each other. Yet, the percentages are different. ![file] , 
 Figure 7D has to be admired for its artistry. ![file] , 
 Figure 8. * Several areas appear to be visible multiple times. Boxes of the same color show several areas that look similar. I left some for Hoya. * If you squint your eyes a bit, you might see several copies of Van Gogh s ear in panel F. ![file] , 
 Also, looking at the Authors Contributions, it appears that no one actually did any experiments. Which would not be out of line with the findings reported above. Could the authors please clarify? ![file] , 
 Also, the study was approved by the  Institutional Review Board and Ethics Committee of the Nanjing University, Jiangsu, China. Which is bewildering, because: 1. no human subjects were used in this study 2. the authors are all affiliated with universities in Changchun, Jilin. ![file] ![file] , 
 What appear to be the same images also appeared in another paper, now retracted:  Retinoic acid-incorporated glycol chitosan nanoparticles inhibit the expression of Ezh2 in U118 and U138 human glioma cells . E.g., that paper s Fig 5: ![] https: www.ncbi.nlm.nih.gov pmc articles PMC4626140 Different authors, at Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu. Published in 2016. , 
 #4 There are similarities between Fig 7D and Fig 4A in a 2015 paper in the Bangladesh J Pharmacol.,  A novel retinoic acid chalcone reverses epithelial-mesenchymal transition in prostate cancer cells . https: www.banglajol.info index.php BJP article download 22602 15729 ![] The authors Jian Zhong and Jian-Quan Hou were affiliated to  Department of Urology, The First Hospital Affiliated to Soochow University, Suzhou, Jiangsu ; and to  Department of Urology, Zhangjiagang Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Suzhou, Jiangsu . ,