Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China.
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Talanta. 2021 Dec 1;235:122817. doi: 10.1016/j.talanta.2021.122817. Epub 2021 Aug 20.
High heterogeneity of hepatocellular carcinoma (HCC) tumor has become an obstacle to select effective therapy for the treatment of HCC patients. Methods that can guide the decision on therapy choice for HCC treatment are highly demanded. Evaluating the drug response of heterogeneous tumor cells at the molecular level can help to reveal the toxicity mechanism of anticancer drugs and provide more information than current cell-based chemosensitivity assays. In the present work, nanostructure-assisted laser desorption/ionization mass spectrometry (NALDI-MS) was used to investigate the lipid response of HCC cells to anticancer drugs. Three types of HCC cells (LM3, Hep G2, Huh7) were treated with sorafenib, doxorubicin hydro-chloride, and cisplatin. We found that the lipid profiles of HCC cells changed a lot after the drug treatment, and the degree of lipid changes was related to the cell viability. Two pairs of fatty acids C16:1/C16:0 and C18:1/C18:0 were found to be strongly related to the viability of HCC cells after drug treatment, and were more sensitive than Methyl-thiazolyl tetrazolium (MTT) assay. Accordingly, they can act as sensitive and comprehensive indexes to evaluate the drug susceptibility of HCC cells. In addition, the peak ratio of several neighboring phospholipids displayed high correlation with drug response of specific cell subtype to specific drug. The ratio of neighboring lipids may be traced back to the activity of enzyme and gene expression which regulate the lipidomic pathway. This method provides drug response of heterogenous tumor cells at molecular level and could be a potential candidate to precise tumor chemosensitivity assay.
肝癌（HCC）肿瘤的高度异质性已成为选择有效治疗方法治疗 HCC 患者的障碍。因此，人们迫切需要能够指导 HCC 治疗方法选择的决策方法。评估异质肿瘤细胞在分子水平上对药物的反应有助于揭示抗癌药物的毒性机制，并能提供比目前基于细胞的化学敏感性测定更丰富的信息。在本工作中，使用纳米结构辅助激光解吸/电离质谱（NALDI-MS）研究了 HCC 细胞对抗癌药物的脂质反应。用索拉非尼、盐酸多柔比星和顺铂处理三种类型的 HCC 细胞（LM3、HepG2、Huh7）。我们发现，药物处理后 HCC 细胞的脂质谱发生了很大变化，脂质变化的程度与细胞活力有关。两对脂肪酸 C16:1/C16:0 和 C18:1/C18:0 被发现与药物处理后 HCC 细胞的活力密切相关，比甲基噻唑基四唑（MTT）测定法更敏感。因此，它们可以作为评估 HCC 细胞药物敏感性的敏感和综合指标。此外，几种相邻磷脂的峰比与特定细胞亚型对特定药物的药物反应高度相关。相邻脂质的比率可能与调节脂质组学途径的酶和基因表达的活性有关。该方法提供了异质肿瘤细胞在分子水平上的药物反应，可能成为精确肿瘤化学敏感性测定的潜在候选方法。
