背景:结直肠癌(CRC)仍然是死亡率的重要因素,经常因转移和化疗耐药而加剧。新的治疗策略对于增强当前的治疗是必要的。PI3K/Akt信号通路的失调与CRC进展有关。这项研究调查了Wortmannin的治疗潜力,结合5-氟尿嘧啶(5-FU),在CRC中靶向PI3K/Akt途径。
方法:通过伤口愈合和MTT试验评估抗迁移和抗增殖作用。使用膜联蛋白V/碘化丙啶凋亡测定来评估凋亡和细胞周期改变。通过ROS检查Wortmannin对氧化剂/抗氧化剂平衡的影响,SOD,CAT,MDA,和T-SH水平。使用RTPCR和蛋白质印迹在mRNA和蛋白质水平分析PI3K/AKT途径的下游靶基因,分别。
结果:Wortmannin显示出对细胞增殖的显著抑制作用,调节幸存者,cyclinD1,PI3K,还有p-Akt.PI3K抑制剂减弱了迁移活性,诱导E-cadherin表达。Wortmannin与5-FU联合诱导细胞凋亡,通过升高的ROS水平增加亚G1细胞。
结论:本研究强调了Wortmannin通过PI3K/Akt通路调节抑制CRC细胞生长和迁移的潜力。它还强调了其作为结直肠癌治疗中有希望的治疗选择的进一步研究的候选人资格。
BACKGROUND: Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of
Wortmannin, combined with 5-fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC.
METHODS: Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay.
Wortmannin\'s impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively.
RESULTS: Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined
Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels.
CONCLUSIONS: This study underscores
Wortmannin\'s potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.