@article{oai:tohoku-mpu.repo.nii.ac.jp:00000735, author = {佐藤, 稔之 and Satoh, Toshiyuki and 立田, 岳生 and Tatsuta, Takeo and 菅原, 栄紀 and Sugawara, Shigeki and 原, 明義 and Hara, Akiyoshi and 細野, 雅祐 and Hosono, Masahiro}, issue = {64}, journal = {東北医科薬科大学研究誌, Journal of Tohoku Medical and Pharmaceutical University}, month = {Dec}, note = {Malignant mesothelioma is one of the aggressive cancer that results most commonly from exposure to asbestos. Treatment options of this cancer are limited even in the case of chemotherapy. Moreover, mesothelioma often becomes resistant to pemetrexed and cisplatin, the key drugs for the mesothelioma treatment. Sialic acid binding lectin isolated from rana catesbeiana oocytes(cSBL)shows remarkable anti-tumor effects caused by its ribonuclease activity in mesothelioma cells and exhibits high synergistic effect with pemetrexed. To find more effective combination regimen of cSBL, we examined currently estimated anti-mesothelioma drugs, TNF-related apoptosis-inducing ligand(TRAIL)and EGF receptor-tyrosine kinase inhibitors(erlotinib, gefitinib, and vandetanib), by using pemetrexed-resistant cell lines, H28-PR and H2452-PR, in vitro. Consequently, the former showed slightly cross-resistance to gefitinib and the latter to cisplatin, cSBL, gefitinib, and vandetanib, respectively. In multiple drugs combination study, pemetrexed+cSBL and pemetrexed+cisplatin+cSBL were higher effective than the other regimens from the aspects of antiproliferative and synergistic effects. Cleavage of Bid and caspase-3 protein which is the sign of apoptosis, and both downregulation of p21 and stabilization of cyclin A which is of cytostatic effects, were detected dependent on the drugs used in the combination treatments. According to these results, we estimated that pemetrexed+cSBL+TRAIL combination showed strong synergy by playing the role without any interference and may serve as a rational regimen with the object of anti-proliferative mechanism. In conclusion, our results indicated that cSBL-containing combination treatments show promise for the treatment of malignant mesothelioma.}, pages = {65--76}, title = {新規抗がん剤候補としてのレクザイムを用いた悪性中皮腫細胞に対する多剤併用効果の検討}, year = {2017}, yomi = {サトウ, トシユキ and タツタ, タケオ and スガワラ, シゲキ and ハラ, アキヨシ and ホソノ, マサヒロ} }