The effects of enoxaparin treatment in a xenograft mouse model of oral squamous cell carcinoma: A pilot study

Author:

Ekici Yeliz1ORCID,Soluk‐Tekkesin Merva2ORCID,Küçüksezer Umut Can3,Celebioglu Hazal Banu Olgun14,Tuncer Erman Bulent5,Bedeloglu Elcin6,Tuncer Feyza Nur4ORCID

Affiliation:

1. Graduate School of Health Sciences, Istanbul University Istanbul Turkey

2. Department of Oral Pathology, Faculty of Dentistry Istanbul University Istanbul Turkey

3. Department of Immunology Aziz Sancar Institute of Experimental Medicine, Istanbul University Istanbul Turkey

4. Department of Genetics Aziz Sancar Institute of Experimental Medicine, Istanbul University Istanbul Turkey

5. Department of Prosthetic Dentistry, Faculty of Dentistry Istanbul Aydin University Istanbul Turkey

6. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Istanbul Aydin University Istanbul Turkey

Abstract

AbstractBackgroundRecent studies suggest that enoxaparin may have therapeutic effects on oral squamous cell carcinoma. We aimed to assess this effect utilizing xenograft mouse model through evaluations of proliferation and angiogenesis markers at the RNA and protein levels.MethodsMice were divided into enoxaparin treatment (n = 4), positive control (n = 4) and negative control (n = 3) groups. Immunohistochemical analyses were performed utilizing Bcl‐2, Bax and Ki‐67 antibodies. Expression levels of proliferation and apoptosis related genes were calculated utilizing qRT‐PCR. Time‐dependent proliferation assays were performed in OSC‐19 and HEK293 cell‐lines.ResultsBax antibody showed positive staining in the cytoplasm and nuclei of tumor cells, while Bcl‐2 antibody displayed staining only in the cytoplasm. A proliferation index of 15%–20% was found in all groups with the Ki‐67 marker indicating no metastasis. Enoxaparin treatment caused decrease in BCL2, BAX and CCNB1 genes' expressions. Compared to HEK293, proliferation assays demonstrated higher division rates in OSC‐19 with a significant decrease in viability after 96 h.ConclusionReduced BCL‐2 expression indicates a regression of tumor growth, but reduced BAX expression is not correlated with increased apoptosis. Despite the aggressive nature of OSC‐19, our results showed a low cell viability with a high division rate when compared with the control HEK293. This paralleled our in vivo findings that showed absence of lymph node metastasis across all mice groups. This discrepancy with the literature suggests that further investigations of the underlying mechanisms and protein‐level analyses are needed to draw definitive conclusions about the effect of enoxaparin on OSC‐19 behavior.

Publisher

Wiley

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