Cross-linked hyaluronic acid gel inhibits metastasis and growth of gastric and hepatic cancer cells: in vitro and in vivo studies
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Ting Lan1, Ji Pang1, Yan Wu1, Miaolin Zhu1, Xiaoyuan Yao4, Min Wu1, Hai Qian1, Zhenyu Zhang2, Jizong Gao3, Yongchang Chen1
1Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, China
2Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital of Capital Medical University, Beijing, China
3R&D Department, BioRegen Biomedical (Changzhou) Co., Ltd., Changzhou, China
4Basic Medical Department, Changchun Medical College, Changchun City, Jilin Province, China
Yongchang Chen, email: firstname.lastname@example.org
Keywords: cross-linked hyaluronic acid gel (CHAG), inhibition, migration, growth, cancer cell
Received: April 09, 2016 Accepted: August 24, 2016 Published: August 31, 2016
Cross-linked hyaluronic acid gel (CHAG) has been used to prevent postoperative adhesion of abdominal tumorectomy. However, its effect on tumor cells is still unknown. This paper was designed to investigate the effect of CHAG on metastasis and growth of tumor cells. Migration and invasion assays, Western blotting, pull down assay, siRNA interference, and nude mice implantation tumor model were applied in this study. The results of in vitro experiments with gastric cancer cell line AGS and hepatic cancer cell line HepG2 showed that CHAG inhibited the migration and invasion activities, the MAPK and PI3K/Akt mediated signaling, the activation of small G proteins Rac1 and RhoA, and the expression of MMPs and PCNA initiated by EGF, through blocking the activation of EGFR. CHAG also had inhibitory effect on activation of other membrane receptors, including integrin and VEGFR. When the expression of hyaluronic acid receptors (CD44 or RHAMM) was interfered, the above inhibitory effects of CHAG still existed. In vivo experimental results showed that CHAG suppressed colonization, growth and metastasis of gastric cancer cell line SGC-7901 in peritoneal cavity of nude mice. In conclusion, CHAG had inhibitory effect on tumor cells, through covering cell surface and blocking the interaction between extracellular stimulative factors and their receptors.
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