title: Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells.
abstract: Hedgehog (Hh) pathway plays a critical role in the progression of prostate cancer (PCa), the most commonly diagnosed non-cutaneous cancer in male adults. Studies showed that di-n-butyl phthalate (DBP) could interference with the Hh pathway. Di-2-ethylhexyl phthalate (DEHP), the congener of DBP, is the major plasticizer used in plastic materials that are inevitably exposed by patients with PCa. The aim of this in vitro study was to investigate whether mono-2-ethyhexyl phthalate (MEHP, the active metabolite of DEHP) could activate the Hh pathway of LNCaP cells. Results showed that the expression of the critical gene of Hh pathway PTCH and androgen-regulated gene KLK3 was significantly decreased on 3, 6 and 9 days with Hh pathway inhibitor cyclopamine's treatment. MEHP notably up-regulated the expression of PTCH with a dose-response relationship in the presence of cyclopamine, which indicate that MEHP might target on the downstream components of Hh pathway and advance the progression of PCa through activating the Hh pathway.
authors.affiliation: WHO Collaborating Center for Research in Human Reproduction, Shanghai Institute of Planned Parenthood Research, Shanghai 200030, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yong
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jiao
authors.affiliation: WHO Collaborating Center for Research in Human Reproduction, Shanghai Institute of Planned Parenthood Research, Shanghai 200030, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Jianhui
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
authors.affiliation: WHO Collaborating Center for Research in Human Reproduction, Shanghai Institute of Planned Parenthood Research, Shanghai 200030, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Qi
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Xiu
authors.affiliation: WHO Collaborating Center for Research in Human Reproduction, Shanghai Institute of Planned Parenthood Research, Shanghai 200030, China. Electronic address: sunzy64@163.com.
authors.forename: Sun
authors.initials: S
authors.lastname: Zuyue
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China. Electronic address: yhzhang@shmu.edu.cn.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yunhui
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D014704:Veratrum Alkaloids; D004051:Diethylhexyl Phthalate; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; C016599:mono-(2-ethylhexyl)phthalate; C000541:cyclopamine
keywords: Hedgehog pathway; LNCaP; MEHP; PTCH; Prostate cancer