title: Combretastatin A4 Regulates Proliferation, Migration, Invasion, and Apoptosis of Thyroid Cancer Cells via PI3K/Akt Signaling Pathway.
abstract: BACKGROUND Combretastatin A4 (CA4) is a potential therapeutic candidate for a variety of human cancer treatments. However, the inhibitive effects of CA4 on thyroid cancer cells are still not well-clarified. This study aimed to investigate the potential effect of CA4 on thyroid cancer cells, as well as underlying mechanism. MATERIAL AND METHODS Human thyroid papillary carcinoma cell line TPC1 was pre-treated with 5 concentrations of CA4 (0, 1, 2, 5, or 10 μM) for 2 h. Cell proliferation was determined by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay. Cell migration and invasion were detected by a modified Boyden chamber assay. Moreover, cell apoptosis was detected by terminal deoxynucleotidyl (TUNEL) staining assay and flow cytometry method. Western blot analysis was performed to determine the expression changes of epithelial-mesenchymal transition (EMT)-related proteins and phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K/Akt) signaling pathway proteins. RESULTS CA4 significantly inhibited the cell proliferation, migration, and invasion, and significantly promoted cell apoptosis in a dose-dependent manner compared with the control group. The EMT-related protein levels of N-Cadherin, Vimentin, Snail1, Slug, Twist1, and ZEB1 were significantly decreased by CA4, while E-cadherin had no significant difference compared with the control group. Moreover, PI3K/Akt signaling pathway protein levels of p-PI3K and p-Akt were significantly decreased, whereas PI3K and Akt had no significant differences compared with the control group. CONCLUSIONS CA4 can inhibit proliferation, migration, and invasion and promote apoptosis of TPC1 cells. These effects might be through the PI3K/Akt signaling pathway. CA4 may be a potential therapeutic target for the treatment of thyroid cancer.
authors.affiliation: Department of General Surgery, Affiliated Gaoming Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland).
authors.forename: Weixin
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of General Surgery, Affiliated Gaoming Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland).
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of General Surgery, Affiliated Gaoming Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland).
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Affiliated Gaoming Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland).
authors.forename: Shangshu
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Affiliated Gaoming Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland).
authors.forename: Weizhao
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Affiliated Gaoming Hospital of Guangdong Medical University, Foshan, Guangdong, China (mainland).
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D013267:Stilbenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C058728:fosbretabulin