Proteomic Analysis of a Human Prostate Cancer Cell Line after Incubation with a Novel Somatostatin14 Derivative

Derivatives of somatostatin (sms) are sometimes used in the treatment of hormone-refractory prostatic cancer, in spite of modest results in controlled clinical studies. The optimal use in this context remains to be determined. The human prostatic cancer cell line LNCaP has been used in several previous proteomic analysis studies, which confirmed that sms indeed can affect the protein expression in this cell line. Proteomic analysis is an important tool to increase the understanding of how sms affects the protein expression of the tumor cell.

In this in vitro study, a new sms14 derivative, smsdx, a conjugate between sms14 and dextran, was incubated with an LNCaP cell culture. Sms14 was used as the positive control. Proteomic analysis, using rapid mini two-dimensional electrophoresis, was performed to determine the effects on protein expression.

Marked quantitative differences were observed in the protein expression profiles in smsdx-treated LNCaP cells compared to negative control cells (untreated cells). Sets of 63 (yet unidentified) protein spots were differentially expressed. The difference was statistically significant (Mann-Whitney analysis). The 63 dataset was used to accurately discriminate control cells from smsdx-treated cells using hierarchical cluster analysis. Both similarities and differences in protein expression were observed between smsdx- and sms14-treated cells.

Smsdx is a new sms14 derivative with long in vivo half-life and pan receptor affinity. Sms14-like effects on the protein expression of LNCaP cells seem to be preserved in the construct. The results convey new information about this potentially useful compound. Further studies are now in progress to identify the affected proteins.