幽门螺杆菌和EB病毒是1类致癌物质，并且它们在胃癌的发生中具有明确的作用。我们之前的研究表明，幽门螺杆菌和EB病毒通过上调癌蛋白Gankyrin可能促进胃癌的进展。天然植物活性分子具有打断癌变的潜力。在本研究中，我们调查了印度人参根提取物（WSE）作为一种可能的化疗药物，用于改变了由幽门螺杆菌和EB病毒共同感染引起的细胞环境的宿主癌蛋白Gankyrin的表达。结果表明，WSE对幽门螺杆菌和EB病毒相关基因转录没有任何抑制作用，除了lmps（lmp1、lmp2a和lmp2B）。此外，WSE通过宿主细胞反应减少了细胞迁移相关基因（mmp3和mmp7）的表达，减低了细胞周期调节基因（pcna）的表达，增加了凋亡抑制基因（bcl2）的表达，提高了凋亡促进基因（apaf1和bax）的表达，以及肿瘤抑制基因（p53、prb和pten）的表达。先静默Gankyrin，然后处理WSE也可降低TNF-ɑ、Akt的表达，提高NFkB、PARP、Casp3和Casp9的表达。WSE还可以减少细胞迁移和基因组不稳定性，并促使细胞进行程序性细胞死亡。此外，分子模拟研究显示，WSE的八种活性化合物中，只有四种化合物与Gankyrin直接稳定相互作用，分别为Withaferin A（WFA）、Withanoside IV（WA4）、Withanolide B（WNB）和Withanolide D（WND）。本文首次报道了WSE处理能通过改变宿主细胞的反应来减少胃上皮细胞中幽门螺杆菌和EB病毒共感染引起的癌变特性。Ramaswamy H. Sarma作为通信作者进行交流。

Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps (lmp1, lmp2a, and lmp2B). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory (mmp3 and mmp7); cell-cycle regulator (pcna); antiapoptotic gene (bcl2); increased the expression of the proapoptotic gene (apaf1 and bax); and tumor suppressor (p53, prb, and pten). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.