Wang Zongze, Li Ying, Zhou Fengxin, Piao Zhe, Hao Jian
Department of Orthopedics, Nankai Hospital of Tianjin, Tianjin 300100, P.R. China.
Renal Department of Internal Medicine, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Oncol Lett. 2018 Aug;16(2):2143-2150. doi: 10.3892/ol.2018.8909. Epub 2018 Jun 6.
The purpose of the present study was to investigate the anticancer effects of β-elemene and paclitaxel for bone neoplasms. MTT assay, reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry and immunostaining were used to analyze the combined effects of β-elemene and paclitaxel both and . The results demonstrated that combined treatment of β-elemene and paclitaxel (β-elemene-paclitaxel) significantly inhibited growth and aggressiveness of U-2OS cells compared with either β-elemene or paclitaxel treatment alone. It was demonstrated that β-elemene promoted paclitaxel-induced apoptosis of U-2OS cells. Anti-apoptosis B-cell lymphoma (Bcl)-2 and Bcl-w genes were downregulated and pro-apoptotic Bcl-2-associated agonist of cell death and caspase-3 genes were upregulated in U-2OS cells following treatment with β-elemene-paclitaxel. Treatment of β-elemene-paclitaxel arrested the cell cycle and decreased cyclin-dependent kinase, cyclin-B1, P21 and P27 expression levels and decreased resistant genes alterations of ATP binding cassette subfamily B member 1, LDL receptor related protein and TS in U-2OS cells. Results demonstrated that β-elemene-paclitaxel decreased G-protein coupled receptor 124 (GPR124), vascular endothelial growth factor receptor, matrix metallopeptidase (MMP)-3, MMP-9 expression levels and increased endostatin, TIMP metallopeptidase inhibitor (TIMP)-1, TIMP-2 expression in U-2OS cells. assay demonstrated that β-elemene-paclitaxel treatment inhibited tumor growth of BALB/c-nu/nu nude mice and prolonged survival rate of tumor-bearing mice. Immunostaining demonstrated that β-elemene-paclitaxel treatment increased apoptotic bodies, GPR124 and increased endostatin, TIMP-1 and TIMP-2 expression in tumor tissues. In conclusion, these results suggest that the combined treatment of β-elemene-paclitaxel is more effective at inhibiting bone neoplasm growth than β-elemene or paclitaxel single treatment GPR124.
本研究的目的是探究β-榄香烯和紫杉醇对骨肿瘤的抗癌作用。采用MTT法、逆转录定量聚合酶链反应、蛋白质免疫印迹法、流式细胞术和免疫染色法分析β-榄香烯和紫杉醇联合使用时的效果。结果表明，与单独使用β-榄香烯或紫杉醇相比，β-榄香烯与紫杉醇联合治疗（β-榄香烯-紫杉醇）显著抑制了U-2OS细胞的生长和侵袭性。结果表明，β-榄香烯促进了紫杉醇诱导的U-2OS细胞凋亡。在用β-榄香烯-紫杉醇处理后的U-2OS细胞中，抗凋亡的B细胞淋巴瘤（Bcl）-2和Bcl-w基因下调，而促凋亡的细胞死亡相关Bcl-2激动剂和半胱天冬酶-3基因上调。β-榄香烯-紫杉醇处理使细胞周期停滞，并降低了细胞周期蛋白依赖性激酶、细胞周期蛋白-B1、P21和P27的表达水平，同时降低了U-2OS细胞中ATP结合盒亚家族B成员1、低密度脂蛋白受体相关蛋白和胸苷酸合成酶耐药基因的改变。结果表明，β-榄香烯-紫杉醇降低了U-2OS细胞中G蛋白偶联受体124（GPR124）、血管内皮生长因子受体、基质金属肽酶（MMP）-3、MMP-9的表达水平，并增加了内皮抑素、金属蛋白酶组织抑制剂（TIMP）-1、TIMP-2的表达。实验证明，β-榄香烯-紫杉醇处理可抑制BALB/c-nu/nu裸鼠的肿瘤生长，并延长荷瘤小鼠的存活率。免疫染色显示，β-榄香烯-紫杉醇处理可增加肿瘤组织中的凋亡小体、GPR124以及内皮抑素、TIMP-1和TIMP-2的表达。总之，这些结果表明，β-榄香烯-紫杉醇联合治疗在抑制骨肿瘤生长方面比β-榄香烯或紫杉醇单一治疗更有效。
