PD98059 通过抑制 ERK 通路和上皮间质转化过程来损害卵巢癌细胞的顺铂耐药性。
PD98059 impairs the cisplatin-resistance of ovarian cancer cells by suppressing ERK pathway and epithelial mesenchymal transition process.
机构信息
Department of Gynecology and Obstetrics, Yantai Yuhuangding Hospital, Yantai 264000, Shandong, China.
Department of Clinical Laboratory, Yantai Yuhuangding Hospital, Yantai 264000, Shandong, China.
出版信息
Cancer Biomark. 2017 Dec 12;21(1):187-194. doi: 10.3233/CBM-170644.
BACKGROUND
The study was aimed at investigating the role of PD98059 on impairing the cisplatin-resistance of ovarian cancer cells and figuring out the potential mechanism.
MATERIAL AND METHODS
Treated with low dose of cisplatin (DDP), DDP-resistant ovarian cancer cells were built and named as SKOV-3/DDP. The cell viabilities of ovarian cancer cell line SKOV-3 and SKOV-3/DDP were detected using MTT assay. Wound healing assay and flow cytometry were performed to detect the migratory ability and cell cycle variation of the two cells and assess the sensibility to DDP in the two cell lines. However, cotreated with DDP and PD98059, cell viability, migration and cell cycle of SKOV-3/DDP were determined again. The DDP-resistance varied a lot and the potential mechanism was studied via western blot assay.
RESULTS
Both treated with DDP, SKOV-3/DDP showed an intense resistance than SKOV-3 including stronger cell viability, larger migration area and less G1/G0 arrest, which confirmed the successfully established DDP-resistant cell line. The phosphorylation of ERK and the activation of epithelial mesenchymal transition (EMT) process contributes to the enhanced resistance. PD98059, a MEK inhibitor, suppresses the ERK pathway and the EMT process of SKOV-3/DDP. Co-treated by DDP and PD98059, cell proliferation and migratory area decreased, meantime more cell were arrested in G0/G1 phase compared to simple treatment of DDP or PD98059.
CONCLUSION
PD98059 efficiently impairs the DDP-resistance of ovarian cancer cells via downregulating the ERK pathway and the EMT process.
背景
本研究旨在探讨 PD98059 对顺铂耐药卵巢癌细胞的作用，探讨其潜在机制。
材料与方法
用低剂量顺铂（DDP）处理，建立 DDP 耐药卵巢癌细胞系 SKOV-3/DDP。采用 MTT 法检测卵巢癌细胞系 SKOV-3 和 SKOV-3/DDP 的细胞活力。采用划痕愈合实验和流式细胞术检测两种细胞的迁移能力和细胞周期变化，评估两种细胞系对 DDP 的敏感性。然而，用 DDP 和 PD98059 共同处理 SKOV-3/DDP 后，再次测定细胞活力、迁移和细胞周期。通过 Western blot 检测探讨 DDP 耐药性差异的潜在机制。
结果
用 DDP 处理后，SKOV-3/DDP 细胞的耐药性明显强于 SKOV-3 细胞，表现为细胞活力更强、迁移面积更大、G1/G0 期阻滞减少，证实了 DDP 耐药细胞系的成功建立。ERK 的磷酸化和上皮间质转化（EMT）过程的激活有助于增强耐药性。MEK 抑制剂 PD98059 抑制 SKOV-3/DDP 的 ERK 通路和 EMT 过程。与单纯 DDP 或 PD98059 处理相比，DDP 和 PD98059 共同处理后，细胞增殖和迁移面积减少，同时更多的细胞停滞在 G0/G1 期。
结论
PD98059 通过下调 ERK 通路和 EMT 过程，有效削弱卵巢癌细胞的 DDP 耐药性。
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