Ling Xiang, Yang Jie, Tan Dongfeng, Ramnath Nithya, Younis Tallal, Bundy Brian N, Slocum Harry K, Yang Lily, Zhou Muxiang, Li Fengzhi
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Lung Cancer. 2005 Sep;49(3):353-61. doi: 10.1016/j.lungcan.2005.03.037.
Although it was observed that inhibition of the antiapoptotic protein survivin expression in lung cancer cells induces apoptosis, the expression and role of survivin variants (survivin-2B and survivin-DeltaEx3) in lung cancer have not yet been characterized. We analyzed 24 non-small-cell lung cancer (NSCLC) samples by semi-quantitative RT-PCR. Surprisingly, our results revealed that high-level expression of survivin-2B is significantly associated with the patient category of "no relapse and alive" (p-value<0.0001). In contrast, high-level expression of survivin-DeltaEx3 is highly associated with the patient category of "relapse and dead" (p-value<0.0001). Consistent with this observation, exogenous expression of survivin-2B in A549 lung cancer cells inhibited cell growth, disrupted the mitochondria potential, and induced apoptotic cell death, while expression of survivin-DeltaEx3 protected the mitochondria potential and facilitated cell survival. These findings provide evidence that survivin-2B and survivin-DeltaEx3 play opposite roles in disease relapse and NSCLC cell survival, which is likely through the differential modulation of mitochondrial potential. Thus, controlling the differential expression of survivin-2B and survivin-DeltaEx3 may represent novel approaches for cancer therapeutics in NSCLC.
虽然观察到肺癌细胞中抗凋亡蛋白生存素表达的抑制会诱导细胞凋亡，但生存素变体（生存素-2B和生存素-ΔEx3）在肺癌中的表达及作用尚未明确。我们通过半定量逆转录聚合酶链反应（RT-PCR）分析了24例非小细胞肺癌（NSCLC）样本。令人惊讶的是，我们的结果显示生存素-2B的高水平表达与“无复发且存活”的患者类别显著相关（p值<0.0001）。相反，生存素-ΔEx3的高水平表达与“复发且死亡”的患者类别高度相关（p值<0.0001）。与这一观察结果一致，在A549肺癌细胞中外源表达生存素-2B会抑制细胞生长、破坏线粒体电位并诱导凋亡性细胞死亡，而生存素-ΔEx3的表达则保护线粒体电位并促进细胞存活。这些发现提供了证据，表明生存素-2B和生存素-ΔEx3在疾病复发和NSCLC细胞存活中发挥相反作用，这可能是通过对线粒体电位的差异调节实现的。因此，控制生存素-2B和生存素-ΔEx3的差异表达可能代表NSCLC癌症治疗的新方法。
