前列腺癌叉头转录因子O4的表达与临床病理关系及其对前列腺癌细胞侵袭的影响

Expression of forkhead transcription factor O4 in prostate cancer and its effect on prostate cancer cell invasion

目的:探讨叉头转录因子O4(forkhead transcription factor O4,FOXO4)在前列腺癌组织中的表达与临床病理的关系及其对前列腺癌细胞侵袭的影响。方法:利用免疫组织化学检测前列腺增生组织及不同临床病理参数的前列腺癌组织FOXO4的表达;Western印迹检测前列腺增生细胞株BPH-1及前列腺癌细胞株PC-3和DU145中FOXO4的表达。对FOXO4表达相对较高的PC-3细胞进行FOXO4 siRNA和杂乱序列siRNA(Scramble siRNA)转染,对FOXO4低表达的DU145细胞进行FOXO4质粒、空白载体转染。利用细胞迁移侵袭试验检测转染后癌细胞的侵袭能力;Western印迹检测转染后癌细胞上皮-间质转化(endothlial-mesenchymal transition,EMT)相关蛋白E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)和波形蛋白(vimentin)的表达。结果:FOXO4在前列腺癌组织及前列腺癌细胞中的表达水平显著低于正常前列腺增生组织及前列腺增生细胞(均P<0.05);前列腺癌特异性抗原(prostate cancer specific antigen,PSA)值<4的前列腺癌组织FOXO4的表达显著高于4≤PSA≤10及PSA>10的癌组织,差异均有统计学意义(均P<0.05);前列腺癌病理分级Gleason评分<8的癌组织FOXO4表达水平明显高于Gleason≥8的癌组织,差异有统计学意义(P<0.05);临床T分期为T1～T2的前列腺癌组织FOXO4表达高于临床T分期为T3～T4的癌组织,差异有统计学意义(P<0.05);无淋巴结转移的前列腺癌组织FOXO4表达明显高于有淋巴结转移的前列腺癌组织,差异有统计学意义(P<0.05)。下调PC-3细胞FOXO4表达水平可显著促进该癌细胞的EMT和E-cadherin表达水平下调,N-cadherin和vimentin表达水平增加,且促进癌细胞侵袭(均P<0.05);上调DU145细胞FOXO4表达水平会抑制该癌细胞的EMT和E-cadherin表达水平上调,N-cadherin和vimentin表达水平下调,且抑制细胞侵袭(均P<0.05)。结论:FOXO4与前列腺癌进展有关,并能通过调节前列腺癌细胞EMT而抑制前列腺癌细胞的侵袭。

Objective: To examine the expression of forkhead transcription factor O4(FOXO4) in prostate cancer and to explore its effect on prostate cancer cell invasion.Methods: Immunohistochemistry was used to detect the expression of FOXO4 in prostate hyperplasia tissues and prostate cancer tissues. Western blot was used to detect the expression of FOXO4 in prostate hyperplasia cell line BPH-1 and prostate cancer cell lines: PC-3 and DU145.PC-3 cells with high relative expression of FOXO4 were transfected with FOXO4 siRNA and scramble siRNA; DU145 cells with low expression of FOXO4 were transfected with FOXO4 plasmid and blank vector. Matrigel Transwell assay was used to detect the invasive ability of transfected cells. The expression of endothelial-mesenchymal transition(EMT)-related proteins E-cadherin, N-cadherin, and vimentin in the transfected cells was detected by Western blot.Results: The expression of FOXO4 in prostate cancer cells and tissues was significantly lower than that in the prostate hyperplasia cells and tissues(both P<0.05). In the prostate cancer tissues,the expression of FOXO4 in cancer tissues with prostate cancer specific antigen(PSA) value <4 was significantly higher than that in the tissues with 4≤PSA≤10 and PSA>10(all P<0.05). The expression of FOXO4 in cancer tissues with Gleason score <8 was significantly higher than that in the cancer tissues with Gleason ≥8(P<0.05). The expression of FOXO4 in clinical stage T1—T2 prostate cancer tissues was higher than that in the clinical stage T3—T4 prostate cancer tissues(P<0.05). The expression of FOXO4 in prostate cancer tissues without lymph node metastasis was significantly higher than that in the prostate cancer tissues with lymph node metastasis(P<0.05).Down-regulation of FOXO4 in PC-3 cells could significantly promote the EMT and invasion, with the decreased expression of E-cadherin and the increased expression of N-cadherin and vimentin(all P<0.05); Up-regulation of FOXO4 in DU145 cells could inhibit the EMT and invasion of cells, with the increased expression of E-cadherin and the decreased expression of N-cadherin and vimentin(all P<0.05).Conclusion: FOXO4 is involved in prostate cancer progression, and it can inhibit prostate cancer cell invasion by regulating EMT of prostate cancer cells.