Maurya Akhilendra Kumar, Vinayak Manjula
a Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science , Banaras Hindu University , Varanasi , India.
Leuk Lymphoma. 2017 May;58(5):1153-1161. doi: 10.1080/10428194.2016.1225207. Epub 2016 Sep 23.
Aberrant activation of PI3K-AKT signaling in many pathological conditions including cancer has attracted much of interest for drug targeting. Various isoforms are known from three classes of PI3K. Targeting selective isoform is advantageous to overcome the global deleterious effects of drug. PI-103 is a specific inhibitor of p110α of class I PI3K. The present study is aimed to analyze anti-carcinogenic activity of PI-103 in Dalton's lymphoma ascite (DLA) cells. Result shows regression in cell proliferation and increased apoptosis in terms of increased Annexin V binding, nuclear fragmentation and active caspase 3 level. It is correlated with attenuation of PI3K-AKT signaling by PI-103 via downregulation of the level of p110α, phospho-p85α, phospho- AKT, and PKCα in DLA cells as well as in HO induced DLA cells. Additionally, ROS accumulation is declined in HO induced DLA cells. Overall result suggests that PI-103 attenuates PI3K-AKT signaling via induction of apoptosis in murine T-cell lymphoma.
在包括癌症在内的许多病理状况下，PI3K-AKT信号通路的异常激活已引起了针对药物靶点的广泛关注。已知PI3K的三类中有多种亚型。靶向选择性亚型有利于克服药物的整体有害影响。PI-103是I类PI3K的p110α的特异性抑制剂。本研究旨在分析PI-103在道尔顿淋巴瘤腹水（DLA）细胞中的抗癌活性。结果显示，就膜联蛋白V结合增加、核碎裂和活性半胱天冬酶3水平升高而言，细胞增殖出现消退且凋亡增加。这与PI-103通过下调DLA细胞以及HO诱导的DLA细胞中p110α、磷酸化p85α、磷酸化AKT和PKCα的水平来减弱PI3K-AKT信号通路相关。此外，HO诱导的DLA细胞中活性氧积累减少。总体结果表明，PI-103通过诱导小鼠T细胞淋巴瘤细胞凋亡来减弱PI3K-AKT信号通路。
