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紫檀芪通过诱导细胞凋亡和阻断细胞周期进展来抑制卵巢癌细胞生长,涉及抑制 STAT3 通路。

Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway.

机构信息

Department of Surgery, Division of Gynecologic Oncology, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Road, Machris 1128, Duarte, CA 91010, USA.

Department of Developmental and Stem Cell Biology, Beckman Research Institute, Duarte, CA 91010, USA.

出版信息

Int J Mol Sci. 2018 Jul 7;19(7):1983. doi: 10.3390/ijms19071983.

Abstract

A growing body of evidence has demonstrated the promising anti-tumor effects of resveratrol in ovarian cancer cells, including its inhibitory effects on STAT3 activation. Nonetheless, the low bioavailability of resveratrol has reduced its attractiveness as a potential anti-cancer treatment. In contrast, pterostilbene, a stilbenoid and resveratrol analog, has demonstrated superior bioavailability, while possessing significant antitumor activity in multiple solid tumors. In this study, the therapeutic potential of pterostilbene was evaluated in ovarian cancer cells. Pterostilbene reduces cell viability in several different ovarian cancer cell lines by suppressing cell cycle progression and inducing apoptosis. Further molecular study has shown that pterostilbene effectively suppressed phosphorylation of STAT3, as well as STAT3 downstream genes that regulate cell cycle and apoptosis, indicating that inhibition of STAT3 pathway may be involved in its anti-tumor activity. The addition of pterostilbene to the commonly used chemotherapy cisplatin demonstrated synergistic antiproliferative activity in several ovarian cancer cell lines. Pterostilbene additionally inhibited cell migration in multiple ovarian cancer cell lines. The above results suggest that pterostilbene facilitates significant anti-tumor activity in ovarian cancer via anti-proliferative and pro-apoptotic mechanisms, possibly via downregulation of JAK/STAT3 pathway. Pterostilbene thus presents as an attractive non-toxic alternative for potential adjuvant or maintenance chemotherapy in ovarian cancer.

摘要

越来越多的证据表明,白藜芦醇在卵巢癌细胞中具有有前途的抗肿瘤作用,包括其对 STAT3 激活的抑制作用。然而,白藜芦醇的低生物利用度降低了其作为潜在抗癌治疗的吸引力。相比之下,白藜芦醇类似物 pterostilbene 具有更高的生物利用度,同时在多种实体肿瘤中具有显著的抗肿瘤活性。在这项研究中,评估了 pterostilbene 在卵巢癌细胞中的治疗潜力。pterostilbene 通过抑制细胞周期进程和诱导细胞凋亡来降低几种不同的卵巢癌细胞系的细胞活力。进一步的分子研究表明,pterostilbene 有效地抑制了 STAT3 的磷酸化以及调节细胞周期和凋亡的 STAT3 下游基因,表明抑制 STAT3 途径可能与其抗肿瘤活性有关。在几种卵巢癌细胞系中,将 pterostilbene 添加到常用的化疗药物顺铂中显示出协同的抗增殖活性。pterostilbene 还抑制了多种卵巢癌细胞系的细胞迁移。上述结果表明,pterostilbene 通过抗增殖和促凋亡机制在卵巢癌中具有显著的抗肿瘤活性,可能通过下调 JAK/STAT3 途径。因此,pterostilbene 作为一种有吸引力的无毒替代品,可用于卵巢癌的辅助或维持化疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5928/6073736/0a6119dffbc2/ijms-19-01983-g001.jpg

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