title: Regulation of chemosensitivity and migration by clusterin in non-small cell lung cancer cells.
abstract: OBJECTIVE
  In terms of drug resistance, cancer cells usually benefit from high clusterin (CLU) expression on chemotherapy. In contrast, CLU expression has been found to be a favorable prognostic factor in lung cancer patients. The aims of this study are to determine the association between CLU expression and chemotherapeutic sensitivity and the potential role of CLU in migration in human non-small-cell lung cancer (NSCLC) cell lines.
  
  
  METHODS
  The levels of clusterin in NSCLC cell lines were altered by short hairpin RNA interference (shRNAi) and overexpression on chemosensitivity assay. Migratory ability of these cell lines was also investigated.
  
  
  RESULTS
  H1355 cells with the highest level of CLU demonstrated the lowest sensitivities to Adriamycin (ADR), docetaxel (DOC), and gemcitabine (GEM) treatment. Inhibition of CLU expression in H1355 cells resulted in higher chemosensitivities. When CLU was stably overexpressed in A549 and H1299 cells, only the chemosensitivity to ADR was reduced. The migratory ability of CLU-overexpressing cells significantly decreased. Moreover, MMP2 transcription was inhibited in CLU-overexpressing H1299 cells. These results indicated lower metastatic potential for cancer cells with high CLU level.
  
  
  CONCLUSIONS
  Lung cancer cells with high level of CLU have reduced chemosensitivity. High level of CLU may result in migratory inhibition and thus favorable prognosis in lung cancer.
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, 135 Nanxiao St., Changhua City, Changhua County 500, Taiwan. 62980@cch.org.tw
authors.forename: Ching-Yuan
authors.initials: CY
authors.lastname: Cheng
authors.forename: Shur-Hueih
authors.initials: SH
authors.lastname: Cherng
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Wu
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Huang
authors.forename: Fu-Tien
authors.initials: FT
authors.lastname: Liao
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Wu
authors.forename: Gwo-Tarng
authors.initials: GT
authors.lastname: Sheu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D051152:Clusterin / Q000235:genetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D034622:RNA Interference; D043823:Taxoids / Q000494:pharmacology; D014158:Transcription, Genetic; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D051152:Clusterin; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D004317:Doxorubicin; D020778:Matrix Metalloproteinase 2; D000093542:Gemcitabine