Korashy Hesham M, Belali Osamah M, Ansar Mushtaq A, Alharbi Naif O
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Anticancer Res. 2016 Nov;36(11):6097-6108. doi: 10.21873/anticanres.11200.
Sunitinib (SUN), a tyrosine kinase inhibitor, is a promising treatment for triple-negative breast cancer (TNBC), the most aggressive and fast-growing type of breast cancer. Yet, the protective effect of SUN against TNBC is poorly investigated and the role of Forkhead box type O (FOXO3a) transcription factor is still unknown.
Cell proliferation was evaluated using the MTT assay. The mRNA and protein expression of apoptotic, oxidative stress and cell cycle genes were determined by real-time polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Percentage of the apoptotic cells were determined by flow cytometry. The role of FOXO3a was knock-downed using siRNA.
SUN caused suppression of MDA-MB231 cell growth associated with induction of apoptosis, cell cycle arrest, oxidative stress markers and FOXO3a gene. Importantly, silencing of FOXO3a mRNA using siRNA significantly rescued MDA-MB231 cells from SUN-induced cell-proliferative arrest.
SUN inhibits TNBC MDA-MB231 cell proliferation through activation of FOXO3a expression.
舒尼替尼（SUN）是一种酪氨酸激酶抑制剂，是治疗三阴性乳腺癌（TNBC）的一种有前景的药物，TNBC是最具侵袭性且生长迅速的乳腺癌类型。然而，SUN对TNBC的保护作用研究较少，叉头框O型（FOXO3a）转录因子的作用仍不清楚。
采用MTT法评估细胞增殖。分别通过实时聚合酶链反应（RT-PCR）和蛋白质免疫印迹分析确定凋亡、氧化应激和细胞周期基因的mRNA和蛋白质表达。通过流式细胞术确定凋亡细胞的百分比。使用小干扰RNA（siRNA）敲低FOXO3a的作用。
SUN导致MDA-MB231细胞生长受到抑制，这与凋亡诱导、细胞周期停滞、氧化应激标志物和FOXO3a基因有关。重要的是，使用siRNA沉默FOXO3a mRNA可显著使MDA-MB231细胞从SUN诱导的细胞增殖停滞中恢复。
SUN通过激活FOXO3a表达抑制TNBC MDA-MB231细胞增殖。
