Hoshida Yujin, Moriyama Masaru, Otsuka Motoyuki, Kato Naoya, Taniguchi Hiroyoshi, Shiratori Yasushi, Seki Naohiko, Omata Masao
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hepatogastroenterology. 2007 Mar;54(74):489-92.
BACKGROUND/AIMS: Only limited patients with hepatoma benefit from chemotherapy without a clear explanation. We aimed to identify genes associated with chemosensitivity using transcriptional profiles.
In 8 hepatoma cells (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2) transcriptional profiles were obtained using cDNA microarray including 2300 genes. Chemosensitivities to 8 anticancer drugs (nimustine, mitomycin C, cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) were measured by obtaining 50% growth inhibitory concentrations (GI50) using MTT assay. Genes having drug-specific association with chemosensitivity were selected.
Up-regulation of topoisomerase II beta was associated with chemo-resistance, the target of doxorubicin. Platinum-specific resistance was associated with superoxide dismutase 2 expression. Antigen peptide transporter 1 expression correlated with nimustine and mitoxantrone-specific susceptibility. These results were verified by semi-quantitative RT-PCR. Drug inactivators reported in non-liver cancers such as multidrug transporters and drug metabolizers showed less diversity of chemosensitivity in hepatoma cells.
To evaluate these gene expressions may be useful to select anticancer drugs, and possibly to consider new therapeutic target to modify drug action.
背景/目的：仅有有限的肝癌患者能从化疗中获益，且原因不明。我们旨在通过转录谱鉴定与化疗敏感性相关的基因。
利用包含2300个基因的cDNA微阵列，获取8种肝癌细胞（HLE、HLF、Huh7、Hep3B、PLC/PRF/5、SK-Hep1、Huh6和HepG2）的转录谱。通过MTT法测定50%生长抑制浓度（GI50），来检测这8种肝癌细胞对8种抗癌药物（尼莫司汀、丝裂霉素C、顺铂、卡铂、阿霉素、表阿霉素、米托蒽醌和5-氟尿嘧啶）的化疗敏感性。选择与化疗敏感性具有药物特异性关联的基因。
拓扑异构酶IIβ的上调与化疗耐药相关，它是阿霉素的作用靶点。铂特异性耐药与超氧化物歧化酶2的表达相关。抗原肽转运体1的表达与尼莫司汀和米托蒽醌特异性敏感性相关。这些结果通过半定量RT-PCR得到验证。在非肝癌中报道的药物灭活剂，如多药转运体和药物代谢酶，在肝癌细胞中化疗敏感性的差异较小。
评估这些基因表达可能有助于选择抗癌药物，并可能有助于考虑新的治疗靶点以改变药物作用。
