Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate cancer cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism.</p><p><b>METHODS</b>PC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot.</p><p><b>RESULTS</b>At 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin.</p><p><b>CONCLUSION</b>Akt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.</p>

Expression of KAI1 in urothelial cancer tissues and its relationship with invasion and metastasis of urothelial cancer / 第二军医大学学报

Objective: To investigate the expression of KAI1 gene in the urothelial cancer tissues and its relationship with the invasion and metastasis of urothelial cancer. Methods: The expression of KAI1 mRNA was detected by real-time fluorescent quantitative(RFQ-PCR) in urothelial cancer tissues and normal mucosa of urinary tract. The KAI1 protein expression was detected by immunohistochemistry(IHC) method in bladder transitional cell carcinoma tissues and the paired normal mucosal tissues. Results: QRT-PCR showed that the average level of KAI1 mRNA in the urothelial cancer tissues was significantly lower than that in the normal bladder tissues (P<0.01); moreover, the increase of pathological grades and clinical stages and the development of lymphatic metastasis were associated with the decrease of KAI1 expression, with significant difference found between the different groups(P<0.05 or P<0.01). The protein expression of KAI1 in the urothelial cancer tissues was significantly lower than that in the normal bladder tissues(P<0.01). The protein expression of KAI1 was decreased with the increase of pathological grades (P<0.05 or P<0.01). We also found that higher expression of KAI1 was associated with superficial invasion (P<0.05) and the presence of lymphatic metastasis (P<0.05). Conclusion: The down-regulation of KAI1 gene is associated with differentiation, infiltration, and lymphatic metastasis of urothelial cancer, which might serve as an effective indicator for malignancy, metastasis and prognosis of urothelial cancer.

Expressions of EphA 2 and KAI 1 in human bladder transitional cell carcinoma and its significance / 肿瘤

Objective: To investigate the association of EphA 2 and KAI 1 protein expressions with the occurrence, invasion, and metastasis of bladder transitional cell carcinoma tissues (BTCC). Methods: The expressions of EphA 2 and KAI 1 proteins were determined by immunohistochemical SP method in 88 cases of BTCC tissues and 76 cases of pericancerous normal bladder tissues. Results: The expression of EphA 2 protein was significantly higher in BTCC tissues than in adjacent normal tissues (P < 0.01). The expression of EphA 2 protein was gradually increased with the elevation of pathological grades of BTCC. The positive rate of EphA 2 expression was significantly higher in deeply infiltrating BTCC than superficially infiltrating BTCC (P < 0.05). It was significantly higher in the group with lymph node metastasis than those without lymph node metastasis (P < 0.05). The expression of KAI 1 protein was significantly lower in BTCC tissues than in adjacent normal tissues (P < 0.01). The expression of KAI 1 was gradually decreased with the elevation of pathological grades of BTCC. The positive rate of KAI 1 expression was significantly lower in deeply infiltrating BTCC than in superficially infiltrating BTCC (P < 0.05). It was significantly lower in the BTCC with lymph node metastasis than those without lymph node metastasis (P < 0.05). A significantly negative correlation was observed between the expression of EphA 2 and that of KAI 1 in BTCC tissues with lymph node metastasis (P < 0.05). Conclusion: Overexpression of EphA 2 and weak expression of KAI 1 may be involved in the tumorigenesis, infiltration, and migration of BTCC.