Effect of camptothecin on collagen synthesis in fibroblasts from patients with keloid.

Abstract

Keloids are distinguished by substantial deposition of collagen in the dermis, resulting in an imbalanced production and aggregation of extra cellular matrix. This study was undertaken to evaluate the effects of the topoisomerase I inhibitor camptothecin (CPT) on collagen synthesis in the activated dermal fibroblasts from healthy donors and patients with keloid. The fibroblasts were cultured in the presence or absence of CPT. Cellular toxicity assay was determined by MTT analysis. The expression of type I collagen and type III collagen was studied both at the transcriptional and post-transcriptional levels, using conventional quantitative real-time reverse transcription PCR and Western blotting. Results showed that there was predominantly a clear and dose-dependent decrease in the synthesis of collagen 1, not collagen 3, in keloid fibroblasts without significantly cellular toxicity. The CPT had an activity on the regulation of the ratio of type I/III collagen in the metabolism of keloid fibroblasts by inhibiting the secretion of type I collagen. The data suggest that the inhibitory effect of CPT, a topoisomerase I inhibitor, on collagen synthesis may be an effective treatment for limiting fibrosis in keloid patients.