Guo J M, Xiao B X, Kang G Z, Liu D H, Chen H, Zhang S, Zhang X N
School of Medicine, Ningbo University, Ningbo 315211, China.
Int J Gynecol Cancer. 2006 Jan-Feb;16(1):341-6. doi: 10.1111/j.1525-1438.2006.00353.x.
Of all neoplasms found in women, cervical cancer has the third highest incidence and causes the fourth most deaths. All-trans retinoic acid (ATRA) may be with chemopreventive potential on cervical cancer, but the mechanisms underlying is not clear. To investigate the mechanisms, human cervical cancer HeLa cells were treated with ATRA for 1, 2, 3, or 4 days in vitro. We found that ATRA inhibited the growth of HeLa cells in a dose-dependent manner at the concentrations from 0.3 to 9.6 mumol/L. Flow cytometric analysis showed that HeLa cells were arrested at G0/G1 phase by ATRA, and the aneuploidy was found when cells were treated for 4 days, which is the first report that ATRA causes aneuploid cycle in HeLa cells. The expression of human telomerase catalytic subunit messenger RNA was decreased remarkably by ATRA. These findings suggested that the inhibition of telomerase activity and arrest of cells at G0/G1 phase might be the key steps through which ATRA inhibits the proliferation of HeLa cells. Our results provide a possible mechanistic explanation for the growth inhibitory effect of ATRA on HeLa cells. Therefore, retinoids may have therapeutic potential to complement current treatments of cervical cancers.
在女性所患的所有肿瘤中，宫颈癌的发病率位居第三，致死率位居第四。全反式维甲酸（ATRA）可能具有预防宫颈癌的潜力，但其潜在机制尚不清楚。为了探究其机制，体外使用ATRA处理人宫颈癌HeLa细胞1天、2天、3天或4天。我们发现，在0.3至9.6μmol/L的浓度范围内，ATRA以剂量依赖的方式抑制HeLa细胞的生长。流式细胞术分析表明，ATRA使HeLa细胞停滞于G0/G1期，并且在处理4天时发现细胞出现非整倍体，这是关于ATRA导致HeLa细胞出现非整倍体周期的首次报道。ATRA显著降低了人端粒酶催化亚基信使RNA的表达。这些发现表明，抑制端粒酶活性以及使细胞停滞于G0/G1期可能是ATRA抑制HeLa细胞增殖的关键步骤。我们的结果为ATRA对HeLa细胞的生长抑制作用提供了一种可能的机制解释。因此，类视黄醇可能具有补充当前宫颈癌治疗方法的治疗潜力。
