CXCR4-mediated Stat3 activation is essential for CXCL12-induced cell invasion in bladder cancer.

CXCL12/CXCR4 signaling plays important roles in tumor cell metastasis in many types of cancers, and CXCR4 is the key regulator of cell motility in bladder cancer. Emerging evidence suggests that transcription-3 (Stat3) activation is associated with bladder cancer cell growth and survival, while the relationship between CXCL12/CXCR4 signal and Stat3 activation remains unclear. In this study, expression analysis of bladder cancer and adjacent normal tissues showed that higher CXCR4 expression was associated with Stat3 phosphorylation. CXCR4 knockdown in bladder cancer T24 cells impaired CXCL12-induced cell invasion and Stat3 activation. Furthermore, blocking Stat3 activity with the chemical inhibitor Stattic inhibited CXCL12-triggered Stat3 phosphorylation and cell invasion in T24 cells, suggesting that Stat3 activation is required for CXCL12 function in the mobility of bladder cancer. Taken together, CXCR4 is necessary for CXCL12 signal transduction in bladder cancer, and CXCL12/CXCR4 promotes invasion of bladder cancer cells through activation of Stat3 transcriptional activity.

[Suppression of invasion and angiogenesis in human prostate cancer PC-3 cells by adenovirus-mediated co-transfer of PTEN and P27].

OBJECTIVE: To investigate the effects of adenovirus-mediated PTEN and P27 on the invasion of PC-3 in vitro and angiogenesis, along with their synergy in the treatment of prostate cancer. METHODS: Recombinant adenovirus vectors of the human tumor suppressor genes PTEN and P27 were constructed. The replication-incompetent recombinant adenovirus was packaged and propagated in HEK293 cells. The viral titer was examined by plaque assay and the mRNA and protein expressions of PTEN and P27 in human prostate cancer cell line PC-3 infected with Ad-PTEN and Ad-P27 were determined by RT-PCR and Western blot respectively. The invasion of PC-3 cells in vitro was examined by Boyden chamber assay. MTT assay was used to testify the effect of supernatant from PC-3 infected with Ad-PTEN and Ad-P27 on the proliferation of endothelial cells ECV-304 and the CAM test was used to testify the effect of PTEN and P27 on angiogenesis. The difference between the combined therapy group and the single gene therapy group was also examined. RESULTS: The viral titers of Ad-PTEN and Ad-P27 were 1.8 x 10(7) pfu/ml and 1.2 x 10(9) pfu/ml respectively. Adenovirus infection verified that the mRNA and protein expression of PTEN and P27 were steady in human PC-3 cells. The invasion in vitro of PC-3 cells was significantly inhibited by infection with Ad-PTEN or/and Ad-P27. CAM and MTT assays of ECV-304 confirmed that the supernatant from PC-3 cells infected with Ad-PTEN or/and Ad-P27 could inhibit the angiogenesis effectively. There was a significant difference between the combined therapy group and the single gene therapy group. CONCLUSION: The combined gene therapy of Ad-PTEN and Ad-P27 plays a synergistic role in inhibiting the invasiveness of PC-3 cells and angiogenesis.

A possible relationship between serum sex hormones and benign prostatic hyperplasia/lower urinary tract symptoms in men who underwent transurethral prostate resection.

In this study, we examined the relationship between sex hormone levels and lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) who underwent transurethral surgery. The study was conducted in 158 patients who came to our hospital for surgery. Clinical conditions were assessed by body mass index (BMI), digital rectal examination, International Prostate Symptom Score (IPSS) and transrectal ultrasound (TRUS). The levels of sex hormones (including total testosterone (TT), estradiol (E 2 ), progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL)) and prostate-specific antigen (PSA) were reviewed. Correlations were determined through statistical analysis. The mean age was 72.06 ± 8.68 years. The total IPSS was significantly associated with the TT level (r = -0.21, P= 0.01). Other sex hormone levels were not correlated with total IPSS. However, some ratios such as E 2 / TT (r = 0.23, P= 0.00) and FSH/LH (r = -0.17, P = 0.04) were associated with total IPSS. Further analysis showed that the nocturia was associated with age (r = 0.16, P= 0.04), BMI (r = 0.21, P = 0.01), and TT (r = -0.19, P= 0.02). Moreover, we divided the patients into two subgroups based on IPSS severity (<20 or ≥20). The mean TT level was in the normal range, but it was significantly related to the presence of severe LUTS. In summary, our study has shown that the severity of LUTS is associated with TT, E 2 / TT and FSH/LH in men who underwent prostate surgery. Increasing nocturia was observed in lower testosterone patients. Additional larger studies are needed to elucidate the potential mechanisms.

[Study of baicalin in inducing prostate cancer cell line DU145 apoptosis in vitro].

OBJECTIVE: The purpose of the present study was to investigate the in vitro effects of baicalin on induction of apoptosis in human prostate cancer cell line DU145. METHOD: Human prostate cancer cell line DU145 was treated with different concentration of baicalin in vitro. The apoptosis rate was determined by FACS analysis, cell cycle distribution was detected by flow cytometry, morphological changes and protein analysis were determined by means of electron microscope techniqueand immunohistochemical techniquerespectively. RESULT: 50micromol x L(-1) and 125 micromol x L(-1) of baicalin dose-dependently induced apoptosis and inhibited the proliferation of prostate cancer cell DU145 in a dose and time-dependent manner. DNA flow cytometric analysis indicated that baicalin induced a arrest in G1 phase, showing a typical apoptosis peak. Electron microscopy detected a characteristic appearance of the apoptotic cells morphology. Immunohistochemical analysis revealed that induction of apoptosis by ways of inhibition of the bcl-2, loss of the Bax, and upregulation of Fas. CONCLUSION: The results indicate that baicalin may induce apoptosis and inhibit proliferation of prostate cancer cells, and has direct anti-tumor effects on human prostate cancer cells.

[PTEN and p27Kip1 have a cooperative role on inhibition proliferation, modulation of cell cycle and inducing apoptosis in prostate cancer PC-3 cell].

OBJECTIVES: To investigate whether the human PC-3 cell infected with recombinant Ad-PTEN and Ad-p27Kip1 can steadily produce PTEN and p27Kip1 protein and change the biologic behaviors such as cell proliferation, cell cycle and apoptosis. The synergistic effect of PTEN and p27Kip1 on the therapy for prostate cancer has also been investigated. METHODS: We constructed recombinant adenovirus vector of human tumor suppressor gene PTEN and p27Kip1. The viral titer was examined by plaque assay and the mRNA and protein expressions of PTEN and p27Kip1 in human prostate cancer cell line PC-3 infected with Ad-PTEN and Ad-p27Kip1 were determined by RT-PCR and Western blot respectively. MTT assay was used to determine the effect of PTEN and p27Kip1 on growth and proliferation of PC-3 cell; the change of cell cycle and apoptosis was examined by flow cytometry, and to compare between the combined therapy group and single gene therapy group. RESULTS: The viral titers of Ad-PTEN and Ad-p27Kip1 were 1.8 x 10(7) pfu/ml and 1.2 x 10(9) pfu/ml respectively. After infected by adenovirus, it had been verified that the mRNA and protein expression of PTEN and p27Kip1 were steady in human PC-3 cell. Ad-PTEN and Ad-p27 Kip1 inhibited the growth and proliferation of PC-3 cells. The progression of cell cycle of PC-3 cell was arrested in G(0)-G(1) phase, meanwhile the apoptosis rate of PC-3 was also affected after Ad-PTEN or/and Ad-p27 Kip1 infected. There was significant difference between combined therapy group and single gene therapy group. CONCLUSION: The recombinant Ad-PTEN and Ad-p27Kip1 vector were constructed successfully and the expression of specific PTEN and p27Kip1 was high, steadily in PC-3 cell line. These results suggested that combination of PTEN with p27Kip1 has an application value in treatment of prostate cancer in future.