title: Blockage of SSRP1/Ets-1/Pim-3 signalling enhances chemosensitivity of nasopharyngeal carcinoma to docetaxel in vitro.
abstract: Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion. Using gene-silencing technology followed by western blot and immunocytochemistry detections, SSRP1 was found to facilitate the translocation of phosphor-Ets-1 from cytoplasm to cell nucleus, but have marginal effect on Ets-1 expression and phosphorylation. Pim-3 was positively regulated by Ets-1. In NPC HNE-1 cells, all SSRP1, Ets-1 and Pim-3 knockdown diminished the cell proliferation, enhanced the apoptosis, as well as inhibited the autophagy, invasion and clonogenicity in the presence or absence of docetaxel at IC25. Exposure of HNE-1 cells to docetaxel (IC25) alone had modest effect on cell proliferation and autophagy, and was not as effective as docetaxel treatment after knockdown of SSRP1, Ets-1 or Pim-3 on induction of the apoptosis and on inhibition of the invasion and clonogenicity. Our data indicate that SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of NPC cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Ai
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Zuozhong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China. Electronic address: tanguolin1234@163.com.
authors.forename: Guolin
authors.initials: G
authors.lastname: Tan
mesh_terms: D001343:Autophagy / Q000235:genetics; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000077143:Docetaxel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009305:Nasopharynx / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D035602:Transcriptional Elongation Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; D006609:High Mobility Group Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; C073537:SSRP1 protein, human; D043823:Taxoids; D035602:Transcriptional Elongation Factors; D000077143:Docetaxel; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Chemosensitivity; Docetaxel; Ets-1; Nasopharyngeal carcinoma; Pim-3; SSRP1