Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway.

Prostate cancer is a common multiple malignant tumor occurring in males. Prostate cancer mortality is the 2nd most common of all tumor types in Western countries and the mortality of morbidity is 13% in the USA. The present study aimed to investigate the anticancer effect of docetaxel on inducing the apoptosis of prostate cancer via the cofilin­1 and paxillin signaling pathway. Treatment with docetaxel (1­50 nM) disposed the human LNCaP prostate cancer cells for 24 h. Cell growth and cytotoxicity were subsequently measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase assay, respectively. Docetaxel-induced cell death was analyzed using flow cytometric and caspase-3 assays. Reverse transcription­quantitative polymerase chain reaction analysis was used to detect the gene expression of cofilin­1 and western blots were used to determine the protein expression of paxillin. Treatment with docetaxel inhibited cell growth, promoted cytotoxicity, activated apoptosis and increased caspase­3 activity in the LNCaP cells. Notably, administration of docetaxel reduced the gene expression of cofilin­1 and the protein expression of paxillin in the LNCaP cells. Additionally, knockdown of cofilin­1 advanced the anticancer effect of docetaxel against LNCaP cells through suppression of the paxillin pathway. The present findings demonstrated that the anticancer effect of docetaxel induces the apoptosis of prostate cancer via the suppression of the cofilin­1 and paxillin signaling pathways, which will assist in setting a stage for the clinical treatment of prostate cancer.

Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3 Cells.

OBJECTIVES: Docetaxel was the first drug with proven survival benefit in men with castration-resistant prostate cancer. Acquired resistance to docetaxel precedes fatality in castration-resistant prostate cancer. The aims of this study were to evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3 cells. METHODS: Docetaxel-resistant PC-3 cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Forty-nine differential proteins were found in docetaxel-resistant PC-3 cells in comparison with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated, whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1 were involved in the formation of tumor vessels; calreticulin, cathepsin D, and cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated protein) and microtubule-associated protein-6 were involved in drug resistance of tumor. CONCLUSION: It is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be helpful for further understanding the molecular mechanisms of docetaxel resistance in PC-3 cells.

[Laparoscopic radical cystectomy with orthotopic ileal neobladder in the treatment of invasive bladder cancer].

OBJECTIVE: To study the technique and outcomes of laparoscopic radical cystectomy (LRC) and evaluate the efficacy of the urinary reservoir constructed with ileum in patients with invasive bladder cancer. METHODS: From 2005 - 2010, A total of 11 patients with bladder cancer were enrolled in this study. Laparoscopy was performed with 5 trocars. Urodynamic examination was performed, the function of upper urinary tract was tested, and complications were evaluated in all the eleven cases. RESULTS: The mean operation time was 420 minutes (ranged 350 to 490 min) and mean blood loss was 410 ml (ranged 300 to 700 ml). Ten of the 11 patients had complete continence, and one case had incontinence. The average flow rate was 11.5 ml/s. The first pressure of the reservoir was 29 cm H2O, and the maximum pressure was 36 cm H2O. The average capacity was 162 ml and 410 ml, respectively. The outlet pressure was 49 cm H2O. The volume of residual urine was 0 - 35 ml. No evidence of ureteral reflux was noted. CONCLUSIONS: Laparoscopic radical cystectomy is a promising method for the treatment of bladder cancer. Orthotopic ileal neobladder is considered as an ideal form of urinary diversion characterized with low pressure, larger capacity and continence.

[Effect of dihydrotestosterone on the transcriptions and expressions of Smad3 and Smad4 in LNCaP cell line].

OBJECTIVE: To investigate the effect of dihydrotestosterone (DHT) on the gene transcriptions and expressions of Smad3 and Smad4 in androgen dependent prostate cancer cell line LNCaP, and whether this effect can be suppressed by the androgen receptor inhibitor flutamide. METHODS: The androgen dependent prostate cancer cell line LNCaP was cultured in RPMI 1640 medium and treated with different concentrations of DHT(2, 10, 50 nmol/L) and flutamide (100 nmol/L). Quantitative reverse transcription PCR (RT-PCR) was used to detect the mRNAs of Smad3 and Smad4. The expressions of Smad3 and Smad4 protein were detected by Western blot assay. RESULTS: Compared with the control group without any DHT or flutamide, higher concentration(10, 50 nmol/L) of DHT enhanced the transcription of Smad3 mRNA (P <0.05). Serial concentrations of DHT increased the expression of Smad3 protein(P < 0.05). Flutamide inhibited the up-regulation of both Smad3 mRNA transcription and expression significantly (P <0.05). 10 nmol/L DHT significantly suppressed the transcription of Smad4 (P <0.05). There was considerable suppressions of Smad4 expression at the presence of DHT in different concentrations (P < 0.05). And the degree of this suppression was more significant than that of DHT on Smad4 mRNA transcription. Flutamide inhibited the suppressive effects of DHT on both Smad4 mRNA transcription and expression. CONCLUSION: DHT can enhance the transcription and expression of Smad3, while it decreases the transcription and expression of Smad4 in LNCaP cell line. There is a possible crosstalk between the AR signal and TGF-beta signal passways at the level of Smads.

[Correlation between EPS composition and elevated serum PSA in prostatitis patients].

OBJECTIVE: To explore the correlation between the content of lecithin mass and white blood cells (WBC) of the expressed prostatic secretion (EPS) and the concentration of serum PSA in patients with prostatitis, and to study the difference in serum PSA concentration between patients with bacterial prostatitis and those with nonbacterial prostatitis. METHODS: The serum PSA concentration in 62 patients with prostatitis and 22 controls were measured with ELISA method. The correlation between the content of lecithin mass and WBC of the EPS and the elevation of serum PSA was analyzed. And the serum PSA concentration of bacterial prostatitis (9 patients) and that of nonbacterial inflammatory prostatitis (53 patients) were compared. RESULTS: The mean concentrations of serum PSA in the prostatitis and the control groups were (1.79 +/- 0.68) microg/L and (0.63 +/- 0.29) microg/L, respectively. The difference of the serum PSA concentration was significant between the prostatitis and the control groups (P < 0.001) as well as between the groups with higher and lower WBC contents in EPS (P < 0.05), but not between the groups with higher (27 patients) and lower (35 patients) lecithin mass contents in EPS (P > 0.05), nor between the groups of bacterial prostatitis and nonbacterial prostatitis (P > 0.05). CONCLUSION: Prostatitis may cause the elevation of serum PSA concentration. The elevated serum PSA correlates with the content of white blood cells in EPS, but not with the content of lecithin mass in EPS, nor with the type of prostatitis, either bacterial or nonbacterial.