Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, 212013, People's Republic of China.
Department of Obstetrics and Gynecology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou City, Jiangsu Province, China.
J Ovarian Res. 2018 Mar 6;11(1):22. doi: 10.1186/s13048-018-0394-z.
The recurrence, metastasis and poor prognosis are important characteristics of ovarian carcinoma (OC), which are associated with exfoliation of cells from the primary tumor and colonization of the cells in pelvic cavity. On the other hand, the life quality of the patients undergoing surgical resection of OC was influenced by postoperative adhesions. Therefore, preventing postoperative implant tumor and adhesion may be effective methods to improve OC treatment. HyaRegen Gel, a cross-linked hyaluronan gel (CHAG), has been widely used as an anti-adhesive agent following pelvic operation in clinic. However, whether it can affect the implantation and growth of OC cells or not is still not clear.
Migration and invasion assays were applied to detect the effect of CHAG on migration and invasion of OC cells. Western blotting was performed to detect the phosphorylation/activation of EGFR and ERK, and the expression of PCNA and MMP7. Pull down assay was used to analyze the effect of CHAG on the activation of small G protein Rac1. Nude mice implantation tumor model was applied to observe the effect of CHAG on implantation tumor of OC cells.
The results of in vitro experiments showed that CHAG suppressed both basic and EGF-induced migration and invasion of OC cells, blocked the activation of EGF-initiated EGFR activation, inhibited downstream signal transduction of EGFR, and decreased expression of proliferation and migration/invasion related proteins. Meanwhile, results of in vivo experiments showed that CHAG not only inhibited the formation of implantation tumor of OC cells but also delayed the of the growth of the tumors.
CHAG inhibited migration, invasion and proliferation of OC cells in vitro, and suppressed development of implantation tumor of OC in vivo. This made it as both anti-tumor and anti-adhesion agents.
卵巢癌(OC)的复发、转移和预后不良是其重要特征,这与肿瘤细胞从原发灶脱落并在盆腔定植有关。另一方面,OC 患者接受手术切除后的生活质量受到术后粘连的影响。因此,预防术后种植瘤和粘连可能是改善 OC 治疗的有效方法。HyaRegen Gel 是一种交联透明质酸钠凝胶(CHAG),已广泛应用于临床盆腔手术后的防粘连剂。然而,它是否能影响 OC 细胞的种植和生长尚不清楚。
迁移和侵袭实验用于检测 CHAG 对 OC 细胞迁移和侵袭的影响。Western blot 检测 EGFR 和 ERK 的磷酸化/激活以及 PCNA 和 MMP7 的表达。下拉实验分析 CHAG 对小 G 蛋白 Rac1 激活的影响。裸鼠种植瘤模型观察 CHAG 对 OC 细胞种植瘤的影响。
体外实验结果表明,CHAG 抑制 OC 细胞的基础和 EGF 诱导的迁移和侵袭,阻断 EGF 起始的 EGFR 激活,抑制 EGFR 的下游信号转导,降低增殖和迁移/侵袭相关蛋白的表达。同时,体内实验结果表明,CHAG 不仅抑制 OC 细胞种植瘤的形成,而且延迟肿瘤的生长。
CHAG 在体外抑制 OC 细胞的迁移、侵袭和增殖,在体内抑制 OC 种植瘤的发展,使其兼具抗肿瘤和防粘连作用。