Renal cell carcinoma (RCC) is the most frequently occurring malignancy of the kidney worldwide. Anti-angiogenic targeted therapies inhibit the progression of RCC, however, limited effects on the invasion or metastasis of tumor cells have been observed. Cyclic AMP responsive element‑binding protein (CREB) is a serine/threonine kinase that has been implicated in the regulation of cell proliferation, apoptosis, cycle progression and metastasis, amongst others. Our previous research demonstrated that phosphorylated CREB (pCREB) was upregulated in human renal cancer cell lines and tissues, and decreased pCREB at the Ser133 site inhibited the growth and metastatic activity of OS‑RC‑2 cells. However, the role of CREB in RCC metastasis requires further investigation. Thus, the present study further investigated the role of CREB in RCC metastasis. The present study demonstrated that knockdown of CREB using small interfering RNA (siRNA) that targeted CREB (siCREB) significantly inhibited the migration and invasion of 786‑O and OS‑RC‑2 cells, however, the opposite effect was observed in ACHN cells. In addition, knockdown of CREB suppressed the expression of matrix metallopeptidase (MMP)‑2/9 and proteins associated with epithelial‑mesenchymal transition (EMT) in 786‑O and OS‑RC‑2 cells, and promoted expression in ACHN cells. Furthermore, the chromatin immunoprecipitation assay indicated that pCREB (Ser133) had a direct interaction with the fibronectin promoter, however, pCREB (Ser133) did not target the vimentin promoter in RCC. Therefore, the results of the present study indicate that CREB regulated metastatic RCC by mediating the expression of MMP‑2/9 and EMT‑associated proteins, however, CREB‑mediated MMP‑2/9 and EMT‑associated protein expression may be induced by different pathways in different RCC cells.

The present study aimed to investigate the effects of cantharidin on cell cycle distribution, the induction of apoptosis, and Notch1 and Jagged1 expression in ACHN and Caki‑1 renal cancer cells. Cell viability assay, flow cytometry, cell cycle and western blot analyses were performed for ACHN and Caki‑1 cells. Immunohistochemistry was used to analyze the expression of Notch1 and Jagged1 in RCC tissues The results demonstrated that treatment with cantharidin exerted a dose‑ and time‑dependent effect on cell viability, apoptosis induction and G2/M phase cell cycle arrest. Exposure of ACHN and Caki‑1 cells to 20 µM cantharidin reduced cell viability to 26 and 32% respectively, after 48 h. In addition, treatment with cantharidin enhanced the number of ACHN and Caki‑1 cells in G2/M phase to 54.62 and 51.88% respectively, as compared with 17.16 and 16.53% in the control groups. In the ACHN and Caki‑1 cells, treatment with cantharidin induced a marked increase in the proportion of apoptotic cells after 48 h. Furthermore, cantharidin enhanced the percentage ACHN and Caki‑1 apoptotic cells to 57.23 and 62.34% respectively, as compared with 2.27 and 3.06% in the control groups. Detection of Notch1 and Jagged1 expression demonstrated that levels were significantly increased in carcinoma tissues. Conversely, cantharidin exhibited an inhibitory effect on Notch1 and Jagged1 expression after 48 h. Therefore, treatment with cantharidin may exert a promising effect on the inhibition of renal cancer, and may be of therapeutic importance for the treatment of renal cancer.

Bladder cancer (BCa) is one of the most common urinary cancers. The present study aims to investigate whether Paeoniflorin (Pae) can exert inhibitory effects on BCa. The results showed that Pae inhibited proliferation of human BCa cell lines in a concentration- and time-dependent manner. Pae and cisplatin (Cis) synergistically inhibited the growth of tumours in RT4-bearing mice. Pae treatment neutralized the body loss induced by Cis. Moreover, Pae induced apoptosis in RT4 cells and increased the activities of caspase3, caspase8 and caspase9. Western blotting and immunohistochemical analysis revealed that the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) level were decreased in Pae-treated RT4 cells and Pae-treated tumour-bearing mice. Furthermore, STAT3 transcriptional target B-cell lymphoma-2 was decreased in Pae-treated RT4 cells. Interestingly, Pae prevented translocation of STAT3 to the nucleus in RT4 cells. Collectively, Pae inhibits the growth of BCa, at least in part, via a STAT3 pathway.

BackgroundMethylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. However, the clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified.MethodsA systematic literature search was performed to identify eligible studies in the PubMed, Embase, EBSCO, CKNI and Wanfang databases. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (95 % CI) was calculated and summarized.ResultsNine eligible studies were included in the present meta-analysis consisting of a total of 1017 bladder cancer patients and 265 non-tumor controls. A significant association was found between CDH13 methylation levels and bladder cancer (OR = 21.71, P < 0.001). The results of subgroup analyses based on sample type suggested that CDH13 methylation was significantly associated with bladder cancer risk in both the tissue and the urine (OR = 53.94, P < 0.001; OR = 7.71, P < 0.001; respectively). A subgroup analysis based on ethnic population showed that the OR value of methylated CDH13 was higher in Asians than in Caucasians (OR = 35.18, P < 0.001; OR = 8.86, P < 0.001; respectively). The relationships between CDH13 methylation and clinicopathological features were also analyzed. A significant association was not observed between CDH13 methylation status and gender (P = 0.053). Our results revealed that CDH13 methylation was significantly associated with high-grade bladder cancer, multiple bladder cancer and muscle invasive bladder cancer (OR = 2.22, P < 0.001; OR = 1.45, P = 0.032; OR = 3.42, P < 0.001; respectively).ConclusionOur study indicates that CDH13 methylation may play an important role in the carcinogenesis, development and progression of bladder cancer. In addition, CDH13 methylation has the potential to be a useful biomarker for bladder cancer screening in urine samples and to be a prognostic biomarker in the clinic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12894-016-0171-5) contains supplementary material, which is available to authorized users.

BackgroundThe vitamin D receptor (VDR) plays a key role in vitamin-mediated signaling pathway. Emerging evidence has suggested that the VDR polymorphism may contribute to the risk of prostate cancer (PCa). However, the existing results are not conclusive in Asian population.MethodsWe aim to evaluate the potential role of VDR polymorphisms on PCa of Asian population. PubMed, Scopus, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wang Fang Data, and VIP Periodical were retrieved, and eligible studies (case–control or cohort study) meeting the inclusion criteria were evaluated through an updated meta-analysis using Stata13.0 software.ResultsA total of 1,363 cases and 2,101 controls obtained from 13 eligible publications were eventually included in this meta-analysis. Our results show that a significant association of VDR taq1 polymorphism with PCa risk, especially in the Japanese population. In the clinical stage-stratified analysis, the pooled results revealed no significant difference in genetic polymorphisms between the local stage and control groups, whereas there was increased frequency of T allele and TT genotype in the advanced tumor stage group compared with local tumor stage or control groups. Similarly, no significant difference was seen in Gleason <7 and control groups, but the T allele and TT genotype were significantly higher in the Gleason ≥7 group compared with Gleason <7 or control groups.ConclusionThe VDR TaqI polymorphism might be associated with PCa risk in Asian population, especially in the Japanese population. Also, PCa patients carrying the T allele or TT genotype were more likely to progress to advanced stage. These results suggest that VDR TaqI polymorphisms may be potential diagnostic biomarkers for PCa susceptibility.