Qingying Wang1, Yingze Wei, Jiawen Zhang. 1. *Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University; and †Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai; and ‡Department of Pathology, Nantong Tumor Hospital, Nantong, China.
Abstract
OBJECTIVE: D-dopachrome tautomerase (D-DT) is a homologue of macrophage migration inhibitory factor (MIF) with similar functions. However, the possible biological roles of D-DT in cervical cancer remain unknown so far. METHODS: D-dopachrome tautomerase was assessed by immunohistochemistry in 83 cervical cancer and 31 normal cervix tissues. The stable knockdown of D-DT and MIF by lentivirus-delivered short hairpin RNA was established, and tumor growth was examined in vitro and in vivo. The effects of D-DT and MIF on the migration and invasion were further detected by wound healing assay and transwell assay. Western blot was used to explore the mechanism of D-DT and MIF in cervical cancer pathogenesis. RESULTS: We found that D-DT was significantly high in cervical cancer, which correlated with lymph node metastasis. The knockdown of D-DT and MIF, individually and additively, inhibited the proliferation, migration, and invasion in HeLa and SiHa cells and restrained the growth of xenograft tumor. The ablation of D-DT and MIF rescued the expression of E-cadherin and inhibited the expression of PCNA, cyclin D1, gankyrin, Sam68, and vimentin, as well as phospho-Akt and phospho-glycogen synthase kinase 3-β. CONCLUSIONS: The inhibition of D-DT and MIF in combination may represent a potential therapeutic strategy for cervical cancer.
OBJECTIVE:D-dopachrome tautomerase (D-DT) is a homologue of macrophage migration inhibitory factor (MIF) with similar functions. However, the possible biological roles of D-DT in cervical cancer remain unknown so far. METHODS:D-dopachrome tautomerase was assessed by immunohistochemistry in 83 cervical cancer and 31 normal cervix tissues. The stable knockdown of D-DT and MIF by lentivirus-delivered short hairpin RNA was established, and tumor growth was examined in vitro and in vivo. The effects of D-DT and MIF on the migration and invasion were further detected by wound healing assay and transwell assay. Western blot was used to explore the mechanism of D-DT and MIF in cervical cancer pathogenesis. RESULTS: We found that D-DT was significantly high in cervical cancer, which correlated with lymph node metastasis. The knockdown of D-DT and MIF, individually and additively, inhibited the proliferation, migration, and invasion in HeLa and SiHa cells and restrained the growth of xenograft tumor. The ablation of D-DT and MIF rescued the expression of E-cadherin and inhibited the expression of PCNA, cyclin D1, gankyrin, Sam68, and vimentin, as well as phospho-Akt and phospho-glycogen synthase kinase 3-β. CONCLUSIONS: The inhibition of D-DT and MIF in combination may represent a potential therapeutic strategy for cervical cancer.