Witort Ewa, Lulli Matteo, Carloni Vinicio, Capaccioli Sergio
University of Florence, Italy.
J Chemother. 2013 Oct;25(5):292-7. doi: 10.1179/1973947813Y.0000000087.
Chemoresistance is a major cause of mortality of patients with advanced and metastatic hepatocellular carcinoma (HCC), the fifth most common cancer in the world. We employed a molecular approach to inhibit cell proliferation and induce apoptosis in HepG2 cells, originated from human hepatocarcinoma. TRADD gene expression was knocked down by an antisense oligonucleotide (ASO TRADD), resulting in TRADD protein decrease by 60%, coinciding with increase of apoptotic cell death of up to 30%. Combination of the ASO TRADD with the cytotoxic drugs 5-fluorouracil or paclitaxel did not improve chemosensitivity of HepG2 cells, while the combined administration of the ASO TRADD with proteasome inhibitors MG132 or ALLN inhibited cell proliferation by 80% and 93%, respectively. Taken together, these findings reveal the importance to combine proteasome inhibitors with silencing of anti-apoptotic signalling components to target HCC cells effectively and provide useful data for developing potential treatments of HCC.
化疗耐药是晚期和转移性肝细胞癌（HCC）患者死亡的主要原因，HCC是全球第五大常见癌症。我们采用分子方法抑制源自人肝癌的HepG2细胞的增殖并诱导其凋亡。反义寡核苷酸（ASO TRADD）敲低TRADD基因表达，导致TRADD蛋白减少60%，同时凋亡细胞死亡增加高达30%。ASO TRADD与细胞毒性药物5-氟尿嘧啶或紫杉醇联合使用并未提高HepG2细胞的化疗敏感性，而ASO TRADD与蛋白酶体抑制剂MG132或ALLN联合给药分别抑制细胞增殖80%和93%。综上所述，这些发现揭示了将蛋白酶体抑制剂与抗凋亡信号成分沉默相结合以有效靶向HCC细胞的重要性，并为开发HCC的潜在治疗方法提供了有用的数据。
