Division of Cell Recognition, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981‑8558, Japan.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12106. Epub 2021 Apr 21.
Malignant pleural mesothelioma (MPM) is a universally lethal type of cancer that is increasing in incidence worldwide; therefore, the development of new drugs for MPM is an urgent task. Bullfrog sialic acid‑binding lectin (cSBL) is a multifunctional protein that has carbohydrate‑binding and ribonuclease activities. cSBL exerts marked antitumor activity against numerous types of cancer cells, with low toxicity to normal cells. Although and studies revealed that cSBL was effective against MPM, the mechanism by which cSBL exerts antitumor effects is not fully understood. To further understand the mechanism of action of cSBL, the present study aimed to identify the key molecules whose expression was affected by cSBL. The present study established cSBL‑resistant MPM cells. Microarray analyses revealed that there were significant pleiotropic changes in the expression profiles of several genes, including multiple genes involved in metabolic pathways in cSBL‑resistant cells. Furthermore, the expression of some members of the aldo‑keto reductase family was revealed to be markedly downregulated in these cells. Among these, it was particularly interesting that cSBL action reduced the level of AKR1B10, which has been reported as a biomarker candidate for MPM prognosis. These findings revealed novel aspects of the effect of cSBL, which may contribute to the development of new therapeutic strategies for MPM.
恶性胸膜间皮瘤（MPM）是一种普遍致命的癌症，其发病率在全球范围内呈上升趋势；因此，开发用于 MPM 的新药是一项紧迫的任务。牛蛙唾液酸结合凝集素（cSBL）是一种具有多功能的蛋白质，具有碳水化合物结合和核糖核酸酶活性。cSBL 对多种癌细胞具有明显的抗肿瘤活性，对正常细胞的毒性较低。虽然 和 研究表明 cSBL 对 MPM 有效，但 cSBL 发挥抗肿瘤作用的机制尚不完全清楚。为了进一步了解 cSBL 的作用机制，本研究旨在鉴定受 cSBL 影响的关键分子。本研究建立了 cSBL 耐药的 MPM 细胞。微阵列分析显示，cSBL 耐药细胞中存在多个基因表达谱的显著多效性变化，包括多个参与代谢途径的基因。此外，还发现醛酮还原酶家族的一些成员在这些细胞中的表达明显下调。在这些基因中，特别有趣的是 cSBL 作用降低了 AKR1B10 的水平，AKR1B10 已被报道为 MPM 预后的生物标志物候选物。这些发现揭示了 cSBL 作用的新方面，可能有助于为 MPM 开发新的治疗策略。
