Jones Hannah M, Fang Ziwei, Sun Wenchuan, Clark Leslie H, Stine Jessica E, Tran Arthur-Quan, Sullivan Stephanie A, Gilliam Timothy P, Zhou Chunxiao, Bae-Jump Victoria L
Division of Gynecologic Oncology, University of North CarolinaChapel Hill, NC, USA.
Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical UniversityBeijing, P. R. China.
Am J Cancer Res. 2017 Dec 1;7(12):2478-2490. eCollection 2017.
Ovarian cancer is the 8th most common cancer in women, and the 5th leading cause of cancer-related deaths among women in the United States. Statins have been shown to have promising anti-tumorigenic activity in many types of cancers. We sought to determine the effects of atorvastatin (ATO) on cell proliferation in ovarian cancer and identify the mechanisms by which ATO inhibits cell growth in this disease. ATO inhibited cell proliferation of both the Hey and SKOV3 ovarian cancer cells in a dose-dependent manner. The anti-proliferative activity of ATO in the ovarian cancer cell lines was associated with induction of apoptosis, autophagy, cellular stress and cell cycle G1 arrest via inhibition of AKT/mTOR and activation of the MAPK pathways. Moreover, ATO inhibited cell adhesion and invasion as well as decreased expression of VEGF and MMP9. c-Myc was downregulated in ovarian cancer cells exposed to ATO. Inhibition of c-Myc by JQ1 synergistically increased the sensitivity of ovarian cancer cells to ATO. This data suggests that ATO may have a therapeutic role in the treatment of ovarian cancer and warrant further exploration in clinical trials.
卵巢癌是女性中第八大常见癌症，也是美国女性癌症相关死亡的第五大主要原因。他汀类药物已被证明在多种癌症中具有有前景的抗肿瘤活性。我们试图确定阿托伐他汀（ATO）对卵巢癌细胞增殖的影响，并确定ATO抑制该疾病细胞生长的机制。ATO以剂量依赖性方式抑制了Hey和SKOV3卵巢癌细胞的增殖。ATO在卵巢癌细胞系中的抗增殖活性与通过抑制AKT/mTOR和激活MAPK途径诱导细胞凋亡、自噬、细胞应激以及细胞周期G1期阻滞有关。此外，ATO抑制细胞黏附和侵袭，并降低VEGF和MMP9的表达。在暴露于ATO的卵巢癌细胞中，c-Myc被下调。JQ1对c-Myc的抑制协同增加了卵巢癌细胞对ATO的敏感性。这些数据表明，ATO可能在卵巢癌治疗中具有治疗作用，值得在临床试验中进一步探索。
