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目的研究SOX4基因在前列腺癌患者中的表达;探讨二烯丙三硫(DATS)对SOX4表达阳性前列腺癌细胞的生物学作用及对SOX4表达的调节作用。方法采用免疫组织化学PV-9000二步法检测141例前列腺癌患者SOX4的表达,观察其与临床病理指标和预后的关联。采用不同浓度(0、20、40、60μmol/L)DATS处理前列腺癌Vcap细胞株,细胞增殖活性MTS法测定Vcap细胞的增殖能力;细胞体外侵袭实验检测40μmol/L DATS对Vcap细胞侵袭能力的作用;实时定量PCR(Real-time PCR)检测40μmol/L DATS作用后,Vcap细胞中SOX4mRNA的表达水平变化。结果 SOX4蛋白在21%(28/135)的前列腺癌患者中过表达,与Gleason评分、远处转移呈正相关(P<0.05)。SOX4是影响患者生存的独立预后因素。体外实验显示,20～60μmol/L DATS对前列腺癌细胞株Vcap的生长有较明显的抑制作用,且呈浓度和时间依赖性。40μmol/L DATS明显抑制Vcap细胞的侵袭能力,并在mRNA水平上下调SOX4的表达。结论 SOX4的过表达提示前列腺癌患者预后不良。DATS抑制前列腺癌Vcap细胞的增殖和侵袭能力,并在mRNA水平上显著下调SOX4的表达。
Objective To study the expression of SOX4 gene in prostate cancer patients and to investigate the biological effect of diallyl trisulfide (DATS) on the SOX4 positive prostate cancer cells and the regulation of SOX4 expression. Methods The immunohistochemical PV-9000 two-step method was used to detect the expression of SOX4 in 141 patients with prostate cancer. The correlation between SOX4 and clinicopathological parameters and prognosis was observed. Prostate cancer Vcap cells were treated with different concentrations of DATS (0, 20, 40 and 60μmol / L), and cell proliferative activity was measured by MTS assay. The in vitro invasion assay was used to detect the effect of 40μmol / L DATS on the invasiveness of Vcap cells Real-time PCR was used to detect the expression level of SOX4 mRNA in Vcap cells after 40μmol / L DATS treatment. Results SOX4 protein was overexpressed in 21% (28/135) of prostate cancer patients, which was positively correlated with Gleason score and distant metastasis (P <0.05). SOX4 is an independent prognostic factor affecting patient survival. In vitro experiments showed that 20 ~ 60μmol / L DATS had a significant inhibitory effect on the growth of prostate cancer cell line Vcap in a concentration- and time-dependent manner. 40μmol / L DATS significantly inhibited the invasion of Vcap cells and down-regulated the expression of SOX4 at the mRNA level. Conclusion Overexpression of SOX4 suggests that patients with prostate cancer have a poor prognosis. DATS inhibits the proliferation and invasion of prostate cancer Vcap cells and significantly down-regulates SOX4 expression at the mRNA level.