Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.
Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.
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DOI：
10.18632/oncotarget.17198
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发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Hosono M
中科院分区：
文献类型：
--
作者：
Satoh T;Tatsuta T;Sugawara S;Hara A;Hosono M
恶性间皮瘤是一种侵袭性癌症，治疗选择有限。牛蛙卵母细胞唾液酸结合凝集素（sialicacid-bindinglectin，cSBL）是一种具有抗癌活性的多功能蛋白。在间皮瘤和正常间皮瘤细胞系中评价了培美曲塞、顺铂和cSBL的作用。我们评价了培美曲塞、顺铂和cSBL单独或联合处理的H28细胞的细胞毒性、细胞凋亡、caspase-3裂解和活化、细胞增殖、细胞周期阻滞和细胞周期蛋白水平。单独用cSBL处理对间皮瘤细胞具有细胞毒性。在更广泛的细胞系中观察到cSBL的抗癌作用，并显示出比培美曲塞或顺铂更大的癌细胞选择性。培美曲塞+ cSBL联合治疗导致的剂量依赖性细胞毒性大于培美曲塞+顺铂（间皮瘤的标准治疗）。培美曲塞+ cSBL的协同作用由培美曲塞的细胞抑制作用和cSBL的细胞毒性作用介导。因此，cSBL似乎具有治疗间皮瘤的治疗潜力。
Malignant mesothelioma is an aggressive cancer with limited therapeutic options. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a multifunctional protein with anti-cancer activity. The effects of pemetrexed, cisplatin, and cSBL were evaluated in mesothelioma and normal mesothelial cell lines. We evaluated cytotoxicity, apoptosis, caspase-3 cleavage and activation, cell proliferation, cell cycle arrest, and levels of cell cycle proteins in H28 cells treated with pemetrexed, cisplatin, and cSBL alone or in combination. Treatment with cSBL alone was cytotoxic to mesothelioma cells. The anti-cancer effect of cSBL was observed in a broader range of cell lines and exhibited greater cancer cell selectivity than pemetrexed or cisplatin. Combination treatment with pemetrexed + cSBL resulted in greater dose-dependent cytotoxicity than pemetrexed + cisplatin, the standard of care in mesothelioma. The synergistic effect of pemetrexed + cSBL was mediated by the cytostatic effect of pemetrexed and the cytotoxic effect of cSBL. It thus appears that cSBL has therapeutic potential for the treatment of mesothelioma.
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