Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

OBJECTIVETo study the effect of Weikangning (WKN) containing serum on growth and cell cycle regulators of gastric cancer cell.

METHODSWKN containing drug serum was prepared by gastric perfusion of WKN in different dosages to SD rats. Gastric cancer cells were cultured in medium contained the drug serum with different concentrations of WKN. The change of cell cycle was detected by flow cytometry, and the mRNA and protein expressions of CyclinD2, CyclinE, Cyclin-dependant kinase2 (CdK2), Cdk4, Cdk6 and p16(INK4a), p27(KIP1) were detected with immunohistochemistry (IHC) SABC method and RT-PCR.

RESULTSAfter WKN intervention, the cancer cells were constrained in stage G0/G1, unable or retardatory to enter stage G (namely, the DNA synthesis stage). IHC examination showed the grey scale values of CyclinD2, CyclinE, Cdk2, Cdk4 and Cdk6 were higher, and that of p27(KIP1) and p16(INK4a) were lower in cells after moderate/high dosage WKN intervention than those in the blank control (P < 0.01); RT-PCR showed the OPTD values of CyclinD2, CyclinE, Cdk2, Cdk4 and Cdk6 were lower, and that of p27(KIP1) and p16(INK4a) were higher in cells after moderate/high dosage WKN intervention than those in the blank control (P < 0.01).

CONCLUSIONWKN can inhibit the expressions of cell cycle promoting related factors of gastric cancer cell, including CyclinD2, CyclinE, Cdk2, Cdk4 and Cdk6, also enhance the expressions of cell cycle inhibiting factors of gastric cancer cell, as p27(KIP1) and p16(INK4a), which may be the mechanism of action of the remedy in preventing the growth of gastric cancer cells.

Animals ; Cell Cycle ; drug effects ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; Male ; Rats ; Rats, Sprague-Dawley ; Serum ; chemistry ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo observe the effect of drug-containing serum of Chinese traditional herbal decoction Weikangning (WKN) on growth of gastric cancer cell, expression of vascular endothelial growth factor (VEGF) and its receptors including KDR and Flt-1.

METHODSA total of 120 male Wistar rats were given high, medium and low-dose WKN. After the drug-containing serum was prepared, the gastric cancer cells MGC-803 of different dose groups were cultured with the drug-containing serum, respectively. The gastric cell growth was observed by using light microscope and flow cytometer,the expression of VEGF and its receptor Flt-1 was detected with SABC immunohistochemistry method and the mRNA expression levels of VEGF and its receptors including KDR and Flt-1 of different groups were detected with reverse transcription-polymerase chain reaction (RT-PCR), respectively.

RESULTSThe gastric cancer cell growth and cell cycle of the three medicated groups were significantly improved as compared with those of the control group (P <0. 01) ,the proportion of cells in G0 - G1 phase was increased,while the cells in S phase were decreased. It was shown that the apoptotic rates were increased in the medicated groups in a dose-dependent manner. The gray scales ( microm(2) ) of VEGF and Flt-1 in high, medium and low dose groups was 182. 44 +/-0. 54,178. 65 +/-0. 56,174. 80 +/-0. 81 and 168. 51 +/- 0. 81,162. 01 +/-0. 52,148. 20 +/-0. 69, respectively vs 147.82 +/-0. 15(P <0.01) and 144.31 +/-0.71 (P <0.01) in the control group. The mRNA expression of VEGF and its receptors significantly decreased in gastric cancer cells after cultured with WKN contained serum (P < 0. 01 ).

CONCLUSIONWKN has inhibitory effects on gastric cancer cell growth and mRNA expression of VEGF as well as its receptors KDR and Flt-1.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Stomach Neoplasms ; drug therapy ; enzymology ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism