Docetaxel is a first-line chemotherapy for the treatment of patients with castration-resistant prostate cancer (CRPC). Despite the good initial response of docetaxel, drug resistance will inevitably occur. Mechanisms underlying docetaxel resistance are not well elaborated. Endothelial cells (ECs) have been implicated in the progression and metastasis of prostate cancer. However, little attention has been paid to the role of endothelial cells in the development of docetaxel resistance in prostate cancer. Here, we sought to investigate the function and mechanism of endothelial cells involving in the docetaxel resistance of prostate cancer. We found that endothelial cells significantly promoted the proliferation of prostate cancer cells and decreased their sensitivity to docetaxel. Mechanistically, basic fibroblast growth factor (FGF2) secreted by endothelial cells leads to the upregulation of ETS related gene (ERG) expression and activation of the Akt/mTOR signaling pathway in prostate cancer cells to promote docetaxel resistance. In summary, these findings demonstrate a microenvironment-dependent mechanism mediating chemoresistance of prostate cancer and suggest that targeting FGF/FGFR signaling might represent a promising therapeutic strategy to overcome docetaxel resistance.

Background Docetaxel is a first-line chemotherapy for the treatment of patients with castration-resistant prostate cancer (CRPC). Despite the good initial response of docetaxel, drug resistance will inevitably occur. Mechanisms underlying docetaxel resistance are not well elaborated. Endothelial cells (ECs) have been implicated in the progression and metastasis of prostate cancer (PCa). However, little attention has been paid to the role of ECs in the development of docetaxel resistance in PCa. Methods Here, we sought to investigate the function and mechanism of ECs involving in the docetaxel resistance of PCa. The 22Rv1 and C4-2B PCa cell lines were cultured with or without human umbilical vein endothelial cells (HUVEC). The proliferation of each PCa cell line was assessed by CCK8 and EdU assays. Cell viability of each PCa cell line treated with docetaxel was evaluated by CCK8. Apoptosis was measured by flow cytometry. Quantitative reverse transcription (RT)-PCR assay was used to determine the expression of ETS related gene (ERG) in each PCa cell line and FGF2 in HUVEC. The proteins including ERG, Caspase3, PARP, Akt, p-Akt, mTOR and p-mTOR were quantified by western blotting. ERG overexpressing C4-2B cells(C4-2B-ERG) were constructed by transfection with pLenti6.3-ERG lentivirus. C4-2B-ERG cells were knocked down by transfecting with ERG siRNAs. Differentially expressed cytokines between the serum-free media from 22Rv1 and 22Rv1/HUVEC co-culture system were detected by human cytokine array and determined by ELISA assay. Tumors were induced in mice by injecting 22Rv1 cells with or without HUVEC and treated with docetaxel. Tumor growth and apoptosis were examined by immunohistochemistry and TUNEL respectively. Results ECs promoted proliferation and inhibited apoptosis in PCa cells (in vitro) and mouse xenograft tumors induced by these cells (in vivo) under docetaxel treatment. ECs secreted FGF2 to induce ERG expression and activate the Akt/mTOR signaling pathway in PCa cells contributing to docetaxel resistance. Blocking FGF2 could reverse the enhancing effects of HUVEC on docetaxel resistance in PCa cells. Inhibition of the Akt/mTOR signaling pathway could alleviate chemoresistance mediated by ERG. Conclusion ECs promote docetaxel resistance via FGF2/ERG/Akt/mTOR signaling pathway in PCa cells. Targeting FGF/ FGFR signaling may represent a promising therapeutic strategy to overcome docetaxel resistance.

Background: Until recently, most enucleation techniques of the prostate were performed with the application of morcellator. We introduce a modified enucleation technique of thulium laser with non-morcellator approach, which is about incising and vaporizing remaining prostate tissue instead of a morcellator.Methods: A retrospective evaluation of 223 patients undergoing ThuLEP from January 2014 to December 2015 was performed in our institution. One hundred five of the patients used morcellator while the other 118 used non-morcellator approach. All patients were assessed with the International Prostate Symptom Score (IPSS), quality of life (Qol), ultrasonography, serum prostate-specific antigen (PSA), maximal urine flow rate (Qmax), and postvoid residual urine volume (PVR). We reassessed these parameters at 1-, 3-, 6-, and 12-months after operation. Operative time, perioperative, and postoperative complications were also recorded.Results: Significant improvement was noted in the IPSS, QoL, Qmax, and PVR in both groups at the 12-month follow-up, and assessment showed no differences in these parameters between the two groups. Comparisons of the total operation time and enucleation time demonstrated no significant differences between the two groups. Our non-morcellator approach needed more time to incise and vaporize the enucleated tissue compared to morcellation when the prostate volume was about 40–80 ml (p < 0.05), while it showed a significant lower rate of superficial bladder injury than using morcellator (p < 0.05). There were no significant differences in other complications between the two groups (p > 0.05).Conclusions: Our modified technique is a safe and effective procedure for the treatment of BPH avoiding the potential complications caused by morcellator.