Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer
Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer
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评估免疫蛋白酶体作为顺铂耐药小细胞和非小细胞肺癌的潜在治疗靶点
DOI：
10.1007/s00280-020-04061-9
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Konno S
中科院分区：
文献类型：
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作者：
Shoji T;Kikuchi E;Kikuchi J;Takashima Y;Furuta M;Takahashi H;Tsuji K;Maeda M;Kinoshita I;Dosaka-Akita H;Sakakibara-Konishi J;Konno S
PurposeWe评估蛋白酶体亚基的表达，以评估是否蛋白酶体可以在顺铂耐药的肺癌cells.MethodsCisplatin-resistant（CR）的变种，建立从三个非小细胞肺癌（NSCLC）细胞系（A549，H1299，和H1975）和两个小细胞肺癌（SCLC）细胞系（SBC 3和SBC 5）。蛋白酶体亚基的表达，免疫蛋白酶体抑制剂的敏感性，和20 S蛋白酶体的蛋白水解活性进行了检查在CR的肺癌细胞株的变种。ResultsAll 5 CR细胞株高表达的免疫蛋白酶体亚基基因，PSMB 8和PSMB 9的一个或两个，而没有明显的趋势，观察组成性蛋白酶体亚基的表达。CR细胞也表达显著更高水平的PSMB 8和PSMB 9蛋白。CR变种的H1299和SBC 3细胞系更敏感的免疫蛋白酶体抑制剂，并有显着更多的蛋白酶体蛋白水解活性比他们的父母people.ConclusionsThe免疫蛋白酶体可能是一个有效的治疗靶点CR肺癌的一个子集。蛋白酶体蛋白水解活性可能是免疫蛋白酶体抑制剂在顺铂耐药SCLC和NSCLC中疗效的预测标志物。
PurposeWe evaluated the expression of proteasome subunits to assess whether the proteasome could be a therapeutic target in cisplatin-resistant lung cancer cells.MethodsCisplatin-resistant (CR) variants were established from three non-small cell lung cancer (NSCLC) cell lines (A549, H1299, and H1975) and two small cell lung cancer (SCLC) cell lines (SBC3 and SBC5). The expression of proteasome subunits, the sensitivity to immunoproteasome inhibitors, and 20S proteasomal proteolytic activity were examined in the CR variants of the lung cancer cell lines.ResultsAll five CR cell lines highly expressed one or both of the immunoproteasome subunit genes,PSMB8andPSMB9, while no clear trend was observed in the expression of constitutive proteasome subunits. The CR cells expressed significantly higher levels of PSMB8 and PSMB9 proteins, as well. The CR variants of the H1299 and SBC3 cell lines were more sensitive to immunoproteasome inhibitors, and had significantly more proteasomal proteolytic activity than their parental counterparts.ConclusionsThe immunoproteasome may be an effective therapeutic target in a subset of CR lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant SCLC and NSCLC.