title: Involvement of ARLTS1 in chemotherapy and apoptosis in ovarian cancer cell line.
abstract: OBJECTIVE
  Recent evidence suggests that ADP-ribosylation factor-like tumor suppressor gene 1(ARLTS1) may act as a tumor suppressor gene. However, its role in tumor chemotherapy remains unclear. The aim of this study is to investigate the effects of ARLTS1 gene in regulation of chemosensitivity in ovarian cystadenocarcinoma cell line SKOV3.
  
  
  METHODS
  We stably expressed wild-type (wt) ARLTS1 and empty vector (neo) in SKOV3 cells. Chemosensitivity test was carried out with four chemotherapeutic agents. Cell proliferation, cycle kinetics and apoptosis were evaluated by MTT assay and flow cytometry. Apoptosis-related proteins caspase-3 and bcl-2 were determined by Western blot analysis.
  
  
  RESULTS
  The proliferation of wtARLTS1 clones was more dramatically inhibited by all the cytotoxic agents than parental cells (P < 0.05). Increased sensitivity to chemotherapy by two to threefolds was detected in wtARLTS1 cells. The rate of apoptosis in wtARLTS1 was 60.2% treated with DDP (10× peak plasma concentration, PPC), which was dramatically higher than that of neo and parental cells (P is 0.017 and 0.020, respectively). Expression of caspase-3 and bcl-2 in parental cells declined modestly when treated with DDP, while in wtARLTS1 clones the expression of caspase-3 and bcl-2 levels declined more dramatically and become undetectable at lower DDP doses (P = 0.023 and <0.001, respectively).
  
  
  CONCLUSIONS
  Our findings suggested that ARLTS1 may facilitate chemosensitivity in ovarian cancer cells by acting synergistic with chemotherapeutic agents to induce the apoptosis signaling pathway and regulate apoptosis-related proteins.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xiao Yun
authors.initials: XY
authors.lastname: Yang
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.forename: Zhi Lan
authors.initials: ZL
authors.lastname: Peng
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin; D053148:Caspase 3; D020727:ADP-Ribosylation Factors; C500039:ARL11 protein, human; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil