TITLE:
Downregulation of Scar Fibroblasts by Antineoplastic Drugs: A Potential Treatment for Fibroproliferative Disorders
AUTHORS:
M. Georgina Uberti, Yvonne N. Pierpont, Rajat Bhalla, Karan Desai, Martin C. Robson, Wyatt G. Payne
KEYWORDS:
Scar Fibroblasts, Antineoplastic Drugs, Fibroproliferative Disorders, Dupuytren’s Disease, Keloid
JOURNAL NAME:
Surgical Science,
Vol.7 No.6,
June
13,
2016
ABSTRACT: The various fibroproliferative disorders affecting humans have in common
excess fibroblast activity and persistent overexpression or dysregulated
activity of transforming growth factor beta (TGF-β). Cancer has many similar characteristics. Antineoplastic drugs
can downregulate fibroblast activity and cytokine growth factors. This study
evaluates the effect of six antineoplastic drugs on keloid and Dupuytren’s disease
fibroblasts. Keloid, normal scar, Dupuytren’s affected palmar fascia, and normal
palmar fascia fibroblasts were grown and seeded into Fibroblast Populated
Collagen Lattices (FPCLs). The FPCLs were treated with one of six
antineoplastic drugs or left untreated as controls. At 7 days, supernatants
were extracted from all FPCLs and assayed for expression of Transforming Growth
Factor beta (TGF)-β1 and
TGF-β2. All six
antineoplastic drugs significantly inhibited FPCL contraction in both
fibroproliferative conditions compared with the untreated controls (p β1 and TGF-β2 expression was
downregulated in the supernatants of all FPCLs by the drug exposure. Cytotoxicity
did not occur in these studies and was not the reason for the results. Although
antineoplastic drugs can have significant side effects when given systemically,
these results may be minimized when given to small areas involved in fibroproliferative
scarring or when given topically or intralesionally. These in vitro results suggest that antineoplastic drugs may have a
utility for treating various fibroproliferative disorders and warrant further
investigation.