Su Xiu-Zhen, Chen Ran, Wang Cai-Bing, Ouyang Xi-Lin, Jiang Yan, Zhu Ming-Yi
Youjiang Medical University for Nationalities, 98 Chengxiang Road, Baise 533000, China.
Anticancer Agents Med Chem. 2019;19(6):792-801. doi: 10.2174/1871520619666190225123003.
Astaxanthin (AST) shows a large range of beneficial effects together with anti-cancer and antioxidation properties. Human Serum Albumin (HSA) is the most abundant protein in blood plasma which plays the role of a depot and transport protein for many exogenous compounds. However, whether HSA could enhance AST-induced cytotoxic effects in human ovarian cancer cells has not been examined to date.
This study aims to explore the anticancer effect and the molecular mechanism of AST combine with HSA induced cytotoxicity in ovarian cancer SKOV3 cells.
The ovarian cancer SKOV3 cells were treated by AST combined with HSA to study the effects of cell proliferation, cell morphology, cell cycle arrest, related protein expression, nuclear transfer, cell migration, and drug-resistant.
Our data confirmed that AST+HSA treatment enhanced the anticancer effects of AST, arrested G1 phase cell cycle and induced apoptosis in SKOV3 cells. AST+HSA induced apoptosis via mitochondrial apoptotic pathways was related to the increased ratio of Bcl-2/Bax and activation of caspase-3. Besides, exposure of cells to AST+HSA triggered the inactivation of NF-κB and activation p53 and MAPKs signaling pathways. Furthermore, AST+HSA significantly overcome the drug-resistant and inhibited the migration of SKOV3 cells.
AST combined treatment with HSA considerably inhibited NF-κB expression and translocation to nucleus, thereby improving the AST-induced cytotoxic effect on SKOV3 cells. These findings may provide rationale to combine AST with HSA for the treatment of ovarian cancer.
虾青素(AST)具有广泛的有益作用,同时具备抗癌和抗氧化特性。人血清白蛋白(HSA)是血浆中含量最丰富的蛋白质,对许多外源性化合物起着储存和转运蛋白的作用。然而,迄今为止尚未研究HSA是否能增强AST对人卵巢癌细胞的细胞毒性作用。
本研究旨在探讨AST联合HSA诱导卵巢癌SKOV3细胞毒性的抗癌作用及分子机制。
用AST联合HSA处理卵巢癌SKOV3细胞,研究其对细胞增殖、细胞形态、细胞周期阻滞、相关蛋白表达、核转运、细胞迁移和耐药性的影响。
我们的数据证实,AST+HSA处理增强了AST的抗癌作用,使SKOV3细胞的G1期细胞周期停滞并诱导凋亡。AST+HSA通过线粒体凋亡途径诱导凋亡与Bcl-2/Bax比值增加和caspase-3激活有关。此外,细胞暴露于AST+HSA会触发NF-κB失活以及p53和MAPKs信号通路激活。此外,AST+HSA显著克服了耐药性并抑制了SKOV3细胞的迁移。
AST与HSA联合处理可显著抑制NF-κB表达及其向细胞核的转位,从而增强AST对SKOV3细胞的细胞毒性作用。这些发现可能为AST与HSA联合治疗卵巢癌提供理论依据。