雄激素受体反义寡核苷酸对前列腺癌细胞生长的抑制作用

Inhibition of prostate cancer cell proliferation by androgen receptor antisense oligodeoxynucleotides

目的 探讨雄激素受体 (AR)反义寡核苷酸 (aODN)对前列腺癌细胞AR表达和生长的抑制作用。 方法 合成 1对AR正、反义寡核苷酸 ,与LNCaP细胞共培养 ,观察LNCaP细胞的增殖情况 ,RT PCR和Westernblot方法检测ARmRNA水平和AR蛋白表达水平。 结果 含ARaODN的培养基培养处于静止期和对数生长期的LNCaP细胞增殖较对照组均明显减慢。RT PCR证实aODN组吸光度A值 (0 .5 3± 0 .18)与ODN组 (1.14± 0 .2 1)差异有显著性意义 (P <0 .0 5 ) ,提示ARaODN可导致LNCaP细胞ARmRNA显著下调。Westernblot分析显示aODN组条带的吸光度A值 (2 6 .35± 1.33)与ODN组 (33.5 1± 1.4 8)之间差异有显著性意义 (P <0 .0 5 ) ,提示ARaODN可下调LNCaP细胞AR蛋白含量。 结论 ARaODN可抑制前列腺癌细胞AR表达并抑制前列腺癌细胞增殖。

Objective To study the inhibition of AR expression and prostate cancer cell proliferation with androgen receptor(AR) antisense oligodeoxynucleotides(aODN). Methods A pair of AR sense and antisense oligodeoxynucleotides was designed and synthesized. LNCaP cells were cultured with AR ODN and AR aODN. The proliferation of the cells was observed and the AR mRNA and AR protein were detected by RT-PCR and Western blot. Results The proliferation of quiescent and logarithmic phase LNCaP cells was inhibited when cultured with AR aODN.RT-PCR showed that the optical density ratio was significantly different between the aODN group(0.53±0.18)and the ODN group(1.14±0.21), P <0.05,demonstrating that AR aODN could down-regulate the level of AR mRNA of LNCaP cells.Western blot showed that the optical density was significantly different between the aODN group(26.35±1.33)and the ODN group(33.51±1.48), P <0.05,demonstrating that AR aODN could reduce the content of AR protein of LNCaP cells. Conclusions AR aODN inhibits the proliferation of LNCaP by suppressing the AR expression.