title: Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis.
abstract: Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, China. Electronic address: twxy@jnu.edu.cn.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Basic Medical Science, Dalian Medical University, 116044, Dalian, China.
authors.forename: Haiyingjie
authors.initials: H
authors.lastname: Lin
authors.affiliation: Central Laboratory of the First Affiliated Hospital of Jinan University, 510630, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Laboratory of the First Affiliated Hospital of Jinan University, 510630, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Central Laboratory of the First Affiliated Hospital of Jinan University, 510630, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: School of Medicine, Jinan University, 510630, Guangzhou, China.
authors.forename: Fenze
authors.initials: F
authors.lastname: Gao
authors.affiliation: Central Laboratory of the First Affiliated Hospital of Jinan University, 510630, Guangzhou, China; School of Pharmacy, Wenzhou Medical University, 325035, Wenzhou, China. Electronic address: shaotsiang@163.com.
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D012799:Sialyltransferases; D002945:Cisplatin; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human
keywords: Chemosensitivity; Cisplatin; Ovarian cancer; ST3Gal3