Peptide Inhibits Growth of Prostate Cancer Cells LNCap in Vitro and ...

[Abstract]

Prostate cancer is the most commonly diagnosed cancer among men in most western countries, and it is the second leading cause of male death from malignant diseases in Europe and in the USA . The incidence is also rapidly increasing in Asian countries. Androgen ablation has been the most frequently used treatment for disseminated prostate cancer, and most patients with a metastatic disease encounter an initial regression in response to this treatment. However, the disease eventually relapses in most patients and progressed to an androgen-independent state, which no longer responds to conventional therapy . Therefore, development of alternative treatment strategies is crucial for improving the survival of androgen-independent prostate cancer.Recently,the directions of tumor therapy primarily focus on cell apoptosis,tumor targeted therapy ,cell factors et al. Among them,cell apoptosis is one of the hotspots. The targets of VEGF and FGF2, restraining tumor-induced angiogenesis, have already become the research hotspots. We successfully designed, expressed a novel polypeptide for anti-prostate cancer and determinated its activity in vitro and vivo, to provide a new strategy and agent for specific treatment of prostate cancer. The polypeptide drug APP216 was designed based on the amino sequences of BH3?K237?DG2 domain and peptide that could be digested by PSA.However, we need individually confirm the anti-tumor effect of single functional peptide for optimizing the polypeptide. The results of our work may provide effective,specific agent and expore the new anti-caner strategy.There are three parts of our study as below:Part 1: Expressions of vascular endothelial growth factor(VEGF) and its receptor (KDR) ,basic fibroblast growth factor(FGF2) and its receptor (FGFR2) in human prostate cancer cell linesAIM To investigate the expressions of vascular endothelial growth factor (VEGF ) and its receptor (KDR)?basic fibroblast growth factor (FGF2) and its receptor (FGFR2) in human prostate cancer cell lines PC3?LNCap and DU145.METHODS Immunohistochemical staining , Western blot and reverse-transcriptase polymerase chain reaction (RT-PCR) were employed to detect the expressions of VEGF and its receptor KDR?basic fibroblast growth factor (FGF2) and its receptor (FGFR2) in three human prostate cancer cell lines, LNCap?PC-3?DU-145. RESULTS All three cell lines expressed VEGF and KDR?FGF2 and FGFR2. However, the expressions had the differences. CONCLUSION The expressions of KDR and FGFR2 suggest that VEGF and FGF2 may be autocrine growth factors for human prostate carcinoma.Part 2: Anti-prostate cancer activity of BH3?DG2 and K237AIM To investigate the efficacy of peptides (BH3?DG2 and K237) on the growth of prostate cancer cell line LNCap. METHODS The laser scanning confocal fluorescence microimaging system was used to confirm the accurate cellular localization of each peptide; Apoptosis of LNCap cells was observed by Hoechst 33258 staining after BH3 treatment; After treating with each peptide at three different amounts, flow cytometry (FCM) was applied to study cell apoptosis (BH3 treatment group) and cell cycle of prostate cancer cell line LNCap; Cell proliferation was determined by MTS/PMS assay . RESULTS The laser scanning confocal fluorescence microimaging system showed that BH3 was located in cell nucleus primarily?DG2 and K237 were accumulated in a nuclear and cytoplasmic distribution; The process of apoptosis was divided into two stages; Flow cytometry confirmed the nature of the BH3-cell cycle arrest and pro-apoptosis?DG2 and K237-cell cycle arrest; MTS/PMS assay showed an antiproliferative effect of BH3 and K237 on human prostate cancer cell lines LNCap in a manner of concentration dependence; DG2 treatment groups have no positive results .CONCLUSION The results of our work may confirm the anti- LNCap effect of each peptide. It would lay a solid foundation for its further application in vivo.Part 3: Influence of BH3?DG2 and K237 on transplanted prostate tumor in athymic mouseAIM To investigate the effects of BH3?DG2 and K237 on prostate cancer LNCap in vivo. METHODS The forty nude mice of xenotransplanted human prostate cancer cell line LNCap were set up. All nude mice were randomly divided into four groups:control group?BH3 treatment group?DG2 treatment group?K237 treatment group. After the treatment, the volume and weight of the tumor was observed. The inhibition rate of the tumor in nude mice was calculated; The expressions of CD34 and microvascular density (MVD) were examined by immunohistochemistry; The HE staining showed whether the peptides have the toxicity effects on the important organs and tumor tissue; Hoechst33258 staining was used to observe the apoptosis of each treatment group.RESULTS The animal experiment showed that there are inhibiting function to the tumor tissues transplanted in nude mice treated by BH3?DG2 and K237 ; MVD in K237 treatment group and DG2 treatment group were less than in BH3 treatment group and control group (p

Title: Peptide Inhibits Growth of Prostate Cancer Cells LNCap in Vitro and in Vivo: An Experimental Study

Category: Tumor Metastasis

Filename: Peptide Inhibits Growth of Prostate Cancer Cells LNCap in Vitro and in Vivo: An Experimental Study.pdf

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