Satoh Toshiyuki, Tatsuta Takeo, Sugawara Shigeki, Hara Akiyoshi, Hosono Masahiro
Department of Clinical Pharmacotherapeutics, Tohoku Medical and Pharmaceutical University, Aobaku, Sendai, Miyagi 981-8558, Japan.
Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Aobaku, Sendai, Miyagi 981-8558, Japan.
Oncotarget. 2017 Jun 27;8(26):42466-42477. doi: 10.18632/oncotarget.17198.
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.
恶性间皮瘤是一种侵袭性癌症，治疗选择有限。从牛蛙卵母细胞中分离出的唾液酸结合凝集素（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细胞系中评估了培美曲塞、顺铂和cSBL的作用。我们评估了单独或联合使用培美曲塞、顺铂和cSBL处理的H28细胞中的细胞毒性、凋亡、半胱天冬酶-3的切割和激活、细胞增殖、细胞周期阻滞以及细胞周期蛋白水平。单独使用cSBL处理对间皮瘤细胞具有细胞毒性。与培美曲塞或顺铂相比，在更广泛的细胞系中观察到了cSBL的抗癌作用，并且表现出更高的癌细胞选择性。培美曲塞+cSBL联合治疗比间皮瘤的标准治疗方案培美曲塞+顺铂产生更大的剂量依赖性细胞毒性。培美曲塞+cSBL的协同作用是由培美曲塞的细胞生长抑制作用和cSBL的细胞毒性作用介导的。因此，cSBL似乎具有治疗间皮瘤的潜力。
