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Abstract
Cancer cell metabolism responsive to androgen deprivation therapy (ADT) may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-deprivation therapy. To investigate the metabolism regulation effects on androgen-independent growth of prostate cancer, an established LNCaP-s cell model that resembles the clinical scenario of castration-resistant prostate cancer (CRPC), was used in this current study. This cell line was cultured from androgen-sensitive LNCaP parental cells, in an androgen-reduced condition, resembling clinical androgen deprivation therapy. To assess the effects of smsDX on the invasiveness of prostate cancer cells we used wound healing assay and Matrigel™ invasion assay. We evaluated differentially expressed proteins of the parental LNCaP cells and LNCaP-s cells after ADT by means of two-dimensional gel electrophoresis (2-DE) followed by MALDI-TOF mass spectrometric analysis. The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with smsDX than they were for control cells treated with vehicle. 56 proteins were found differentially expressed in LNCaP-s cells compared to LNCaP cells, majority of them were down-regulated after ADT treatment. 104 proteins of LNCaP cells and 86 in LNCaP-s cells, separately, were found differentially expressed after treatment with smsDX, When we explored these protein functions within the website UniProtKB/Swiss-Prot, surprisingly, most of the proteins were found to be involved in the cellular metabolism and mitochondrial function regulation. LNCaP-s as potential metastatic androgen-independent cancer cells, its metabolism and mitochondrial functions could be altered by a new somatostatin derivative smsDX, the smsDX regulatory effects on metabolism in LNCaP-s deliver more therapeutic information with the treatment of CRPC.
Highlights
Prostate cancer is the most common malignancy in men, and the leading cause of cancer-related mortality in US and Europe males [1]
Using LNCaP and LNCaP-s cells to examine the proteins involving in the cell metabolism and energy functions in prostate cancer and to determine the regulatory effects caused by somatostatin derivative smsDX, we demonstrated androgen deprivation therapy (ADT) downregulates most of mitochondrial proteins, possibly results in the activation of mitochondrial-mediated apoptotic pathway
NE cells are characterized by a neuronal-like phenotype which produce and secrete a series of neuropeptides involved in tumor proliferation, transformation and metastasis [19]
Summary
Prostate cancer is the most common malignancy in men, and the leading cause of cancer-related mortality in US and Europe males [1]. The tumor progression to CRPC stage is a complex process that may be involving both clonal selection and adaptive mechanisms in heterogeneous tumors composed of cells that respond differently to androgen deprivation therapy (ADT). The mechanisms by which tumors acquire androgen independence remain unclear and need to be addressed before effective treatment strategies can be developed. Somatostatin analogs bind to SSTRs and are believed to have dual antitumor activity, both direct (anti-proliferative) and indirect (inhibition of various peptide hormones secreted by the tumor cells) [8,9]. Somatostatin analog, lanreotide has been demonstrated to have considerable antineoplastic effect in various tumors, including CRPC [10]. The regulation of somatostatin analog on prostate cancer cellular metabolism has not been clearly addressed
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