Etoposide (VP-16)-induced Apoptosis in Human Non-small Cell Lung Cancer Cells Lacking Endogenous

Abstract

VP-16是一種廣泛被使用的抗癌藥劑，其主要的作用機制是抑制topoisomerase IIα的活性，阻斷DNA的複製，造成腫瘤細胞生長停滯甚至死亡，以達到消滅腫瘤的目的。本研究發現低劑量(5 µM) VP-16可以誘導p53基因缺失的非小細胞肺癌細胞株(NSCLC) H1299的細胞凋亡(apoptosis)。實驗證明VP-16誘導H1299在凋亡的過程中，caspase酵素群扮演相當重要的角色，進一步的分析也發現caspase的活化與凋亡的過程密切關聯(caspase-dependent)。綜合而論，低劑量VP-16誘導p53基因缺失H1299細胞的凋亡模式中，caspase-9可能參與細胞凋亡早期誘導作用，而caspase-7則與凋亡晚期的DNA片段化(fragmentation)有關，試驗中並得知caspase-7抑制劑無法阻止細胞凋亡，推論VP-6除了誘導caspase活化所引起細胞凋亡，同時也活化其他因子參與凋亡的過程。

VP-16 (etoposide), an inhibitor of topoisomerase IIα, was widely used for cancer therapy. We found low dosage of VP-16 causes apoptosis in cancer cells without functional p53. In this work, we have identified that caspases were responsible for the progression of apoptosis in VP-16-induced H1299 cells lacking endogenous p53. Further study showed that apoptosis effectors caspase-9 and caspase-7 were activated prior to apoptosis. This work also demonstrated that VP-16-induced apoptosis in human non-small cell lung cancer cells is independent of p53 status.