Oncotarget

Research Papers:

Sirolimus-eluting stents: opposite in vitro effects on the clonogenic cell potential on a long-term exposure

Francesco Vasuri, Alessio Degiovanni, Mauro Gargiulo, William G. Thilly, Elena V. Gostjeva, Gianandrea Pasquinelli _ and Silvia Fittipaldi

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Oncotarget. 2020; 11:2973-2981. https://doi.org/10.18632/oncotarget.27554

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Abstract

Francesco Vasuri1, Alessio Degiovanni1, Mauro Gargiulo3, William G. Thilly2, Elena V. Gostjeva2, Gianandrea Pasquinelli1 and Silvia Fittipaldi1,2

1 Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University, Bologna, Italy

2 Laboratory in Metakaryotic Biology (LIMB), Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

3 Vascular Surgery Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University, Bologna, Italy

Correspondence to:

Gianandrea Pasquinelli,email: gianandr.pasquinelli@unibo.it

Keywords: atherosclerosis; cell proliferation; sirolimus; stents

Abbreviations: DES: drug-eluting stents; DMSO: dimethyl sulfoxide; mTOR: mammalian target of Rapamycin; SES: sirolimus-eluting stent

Received: February 11, 2020     Accepted: March 19, 2020     Published: August 04, 2020

ABSTRACT

We evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.

Three cells lines (WPMY-1 myofibroblasts, HT-29 colorectal adenocarcinoma, and U2OS osteosarcoma) were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus. The number of colonies and the number of cells per colony were counted.

As main result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus (p = 0.0011), while the number of U2OS colonies progressively decreased (p = 0.0011). The clonal capacity of HT-29 was not modified by the exposure to sirolimus (p = 0.6679).

In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types. In the practice, the plaque typology and composition may influence the response to sirolimus and thus the effectiveness of eluted stent.


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