SBF-1 preferentially inhibits growth of highly malignant human liposarcoma cells
SBF-1 preferentially inhibits growth of highly malignant human liposarcoma cells
复制标题
SBF-1优先抑制高度恶性的人脂肪肉瘤细胞的生长。
DOI：
10.1016/j.jphs.2018.10.009
复制
发表时间：
2018-12-01
影响因子：
3.5
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
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作者：
Chen, Wei;Qian, Xuelong;Xu, Qiang
人类脂肪肉瘤通常涉及频繁的局部复发和转移，但管理是一个挑战。迫切需要改进有效的治疗方法。在本研究中，我们报道了一种甾体皂苷SBF-1在体内外对培养的高度恶性的人脂肪肉瘤SW872-S细胞的生长抑制作用。SBF-1下调蛋白激酶B(AKT)的磷酸化，从而减少细胞与纤维连接蛋白和层粘连蛋白的黏附。随后我们发现SBF-1抑制了SW872-S细胞中氧固醇结合蛋白的表达，提示氧固醇结合蛋白可能参与了恶性脂肪肉瘤细胞的生存。体外培养的SW872-S细胞中，OSBP被抑制后，癌细胞的生长和AKT的磷酸化均受到明显的抑制。综上所述，这些结果表明，SBF-1使SW872-S细胞的OSBP功能明显丧失，从而导致生长抑制。根据我们的发现，OSBP是人类脂肪肉瘤的潜在治疗靶点。(C)2018年作者。由爱思唯尔B.V.代表日本药理学会制作和主办。
Frequent local recurrence and metastasis are generally involved in human liposarcoma, but the management is a challenge. There is an urgent need for improved effective therapy. In the present study, we reported that SBF-1, a steroidal glycoside, inhibited the growth of cultured highly malignant human liposarcoma SW872-S cells in vitro and in vivo. SBF-1 down-regulated the phosphorylation of protein kinase B (AKT) and thus reduced cell adhesion to fibronectin and laminin. Then we found that SBF-1 inhibited the expression of oxysterol binding protein (OSBP) in SW872-S cells, indicating that OSBP may be involved in malignant liposarcoma cell survival. Cancer cell growth and AKT phosphorylation were inhibited significantly upon knockdown of OSBP in SW872-S cells in vitro. Taken together, these results suggest that SBF-1 causes an apparent loss of OSBP function in SW872-S cells, resulting in growth inhibition. Based on our findings, OSBP serves as a potential therapeutic target for human liposarcoma. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.