Wang Qiang, Shi Wei
Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, Shandong 130000, P.R. China.
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Oncol Lett. 2019 Mar;17(3):2976-2982. doi: 10.3892/ol.2019.9890. Epub 2019 Jan 4.
Ovarian cancer is the gynaecological malignancy with the highest mortality rate worldwide, and effective and safe therapeutic methods are limited. UNBS5162, a derivative of naphthalimide, has a clear inhibitory effect on the proliferation of various tumour cells and as a pan-antagonist of CXC chemokine ligand expression, but whether it serves a function in ovarian cancer remains unclear. The aim of the present study was to determine the effects of UNBS5162 on the proliferation, migration and invasion of ovarian cancer cells. The cell viability was detected using a Cell Counting Kit-8 (CCK-8) assay. The invasion and migration of SKOV3 cells were determined using Transwell assays. Cell apoptosis was determined using flow cytometry. The apoptosis-associated proteins and associated factors, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway members, were detected using western blot analysis. The CCK-8 assay revealed that SKOV3 cell viability was affected by UNBS5162 in a dose- and time-dependent manner. In Transwell assays, UNBS5162 inhibited cell invasion and migration. Furthermore, it was identified that UNBS5162 markedly increased the apoptosis rate of SKOV3 cells. Simultaneously, the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was decreased and the expression of the pro-apoptotic proteins active caspase-3 and Bcl-2-associated X protein were increased in SKOV3 cells treated with UNBS5162. In addition, the expression levels of phospho (p-)AKT/total AKT, p-mammalian target of rapamycin (mTOR)/total mTOR, p-p70 S6 kinase (p70S6K)/total p70S6K and cyclin D1 were decreased in the UNBS5162-treated group. The results of the present study indicated that UNBS5162 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells, which may be regulated by the PI3K/AKT signalling pathway. These results suggest that UNBS5162 may be a potential novel drug for clinical ovarian cancer treatment.
卵巢癌是全球死亡率最高的妇科恶性肿瘤,有效的安全治疗方法有限。萘酰亚胺衍生物UNBS5162对多种肿瘤细胞的增殖具有明显的抑制作用,并且作为CXC趋化因子配体表达的泛拮抗剂,但它在卵巢癌中是否发挥作用仍不清楚。本研究的目的是确定UNBS5162对卵巢癌细胞增殖、迁移和侵袭的影响。使用细胞计数试剂盒-8(CCK-8)检测细胞活力。使用Transwell检测法测定SKOV3细胞的侵袭和迁移能力。使用流式细胞术测定细胞凋亡。使用蛋白质免疫印迹分析检测凋亡相关蛋白和相关因子,如磷酸肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路成员。CCK-8检测显示,SKOV3细胞活力受到UNBS5162的剂量和时间依赖性影响。在Transwell检测中,UNBS5162抑制细胞侵袭和迁移。此外,发现UNBS5162显著提高了SKOV3细胞的凋亡率。同时,在用UNBS5162处理的SKOV3细胞中,抗凋亡蛋白B细胞淋巴瘤2(Bcl-2)的表达降低,促凋亡蛋白活化半胱天冬酶-3和Bcl-2相关X蛋白的表达增加。此外,在UNBS5162处理组中,磷酸化(p-)AKT/总AKT、磷酸化雷帕霉素哺乳动物靶蛋白(mTOR)/总mTOR、磷酸化p70核糖体蛋白S6激酶(p70S6K)/总p70S6K和细胞周期蛋白D1的表达水平降低。本研究结果表明,UNBS5162抑制卵巢癌细胞的增殖、迁移和侵袭,并诱导其凋亡,这可能受PI3K/AKT信号通路调控。这些结果表明,UNBS5162可能是一种潜在的新型临床卵巢癌治疗药物。