We previously found that ginsenoside 20(S)-Rg3 diminishes the proliferative and invasive capacities of ovarian cancer cells by decreasing miR-4425 level. Yet the mechanism of action of miR-4425 in ovarian cancer remains unclear. Here we report that miR-4425 is upregulated in ovarian cancer tissues relative to normal ovarian tissues, and transfection of miR-4425 inhibitor impairs the proliferation, migration and invasion of SKOV3 and 3AO ovarian cancer cells. Further, miR-4425 antagomiR reduces cell proliferation in a subcutaneous SKOV3 xenograft model using BALB/c nude mice. We identifies farnesyl-diphosphate farnesyltransferase 1 (FDFT1) as a direct target of miR-4425 by Western blotting and a luciferase reporter assay. Forced expression of FDFT1 via transfection of an FDFT1-expressing plasmid into ovarian cancer cells not only retards cell proliferation, motility and invasiveness, but also negates the tumorigenic properties of a miR-4425 mimic. By contrast, silencing of FDFT1 by siRNAs abrogates suppression of the proliferation, migration and invasion of ovarian cancer cells treated with a miR-4425 inhibitor. Finally, transfection of either a miR-4425 mimic or FDFT1 siRNAs into 20(S)-Rg3-treated ovarian cancer cells counteracts the tumor-inhibitory activity of the ginsenoside. In conclusion, 20(S)-Rg3 exerts anti-ovarian cancer activity by downregulating oncogenic miR-4425 that inhibits the expression of the tumor suppressor gene FDFT1. These results expand our current understanding of the molecular pathways leading to ovarian cancer progression, and unveil the mechanism of action of 20(S)-Rg3 in ovarian cancer inhibition.

我们以前发现人参皂甙20（S）-Rg3通过降低miR-4425水平来降低卵巢癌细胞的增殖和侵袭能力。尚不清楚miR-4425在卵巢癌中的作用机制。在这里我们报道，相对于正常卵巢组织，miR-4425在卵巢癌组织中上调，并且miR-4425抑制剂的转染损害SKOV3和3AO卵巢癌细胞的增殖，迁移和侵袭。此外，使用BALB / c裸鼠，miR-4425 antagomiR减少了皮下SKOV3异种移植模型中的细胞增殖。我们通过蛋白质印迹和荧光素酶报告基因分析鉴定法呢基二磷酸法呢基转移酶1（FDFT1）作为miR-4425的直接目标。通过将表达FTFT1的质粒转染到卵巢癌细胞中来强制表达FDFT1不仅会延迟细胞增殖，运动性和侵袭性，而且会否定miR-4425模拟物的致瘤特性。相比之下，siRNA使FDFT1沉默消除了对用miR-4425抑制剂治疗的卵巢癌细胞的增殖，迁移和侵袭的抑制。最后，将miR-4425模拟物或FDFT1 siRNA转染到20（S）-Rg3处理的卵巢癌细胞中，抵消了人参皂甙的肿瘤抑制活性。总之，20（S）-Rg3通过下调抑制肿瘤抑制基因表达的致癌miR-4425发挥抗卵巢癌活性。siRNA使FDFT1沉默，从而消除了用miR-4425抑制剂处理的卵巢癌细胞的增殖，迁移和侵袭抑制。最后，将miR-4425模拟物或FDFT1 siRNA转染到20（S）-Rg3处理的卵巢癌细胞中，抵消了人参皂甙的肿瘤抑制活性。总之，20（S）-Rg3通过下调抑制肿瘤抑制基因表达的致癌miR-4425发挥抗卵巢癌活性。siRNA使FDFT1沉默，从而消除了用miR-4425抑制剂处理的卵巢癌细胞的增殖，迁移和侵袭抑制。最后，将miR-4425模拟物或FDFT1 siRNA转染到20（S）-Rg3处理的卵巢癌细胞中，抵消了人参皂甙的肿瘤抑制活性。总之，20（S）-Rg3通过下调抑制肿瘤抑制基因表达的致癌miR-4425发挥抗卵巢癌活性。FDFT1。这些结果扩大了我们目前对导致卵巢癌进展的分子途径的了解，并揭示了20（S）-Rg3在卵巢癌抑制中的作用机理。