title: Human papillomavirus type 16-immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype.
abstract: Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is a highly effective chemotherapeutic agent against cervical cancer, but drug resistance is a major obstacle in its clinical application. The mechanism of drug resistance in human cervical cancer is not well understood. Here, we established an in vitro endocervical, cisplatin-resistant cell system that mimics the development of cisplatin resistance in the human cervix. Human papillomavirus (HPV) type 16-immortalized human endocervical cells (HEN-16-2) were treated with cisplatin, and the cisplatin-selected cells (HEN-16-2/CDDP) were resistant to cisplatin, paclitaxel, actinomycin D, doxorubicin, etoposide, and 5-fluorouracil, thus demonstrating a multidrug resistance (MDR) phenotype. Furthermore, compared with a similar passage of drug-sensitive HEN-16-2 cells, HEN-16-2/CDDP cells exhibited the general growth characteristics of cancer cell lines: faster growth in medium containing serum and high calcium levels, higher saturation density, anchorage-independent growth, and formation of tumors in nude mice. These results provided the first in vitro evidence that cisplatin selection can transform HPV-immortalized endocervical cells and cause a phenotype of MDR.
authors.affiliation: Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Ding
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Chernenko
authors.forename: S C
authors.initials: SC
authors.lastname: Tang
authors.forename: A
authors.initials: A
authors.lastname: Pater
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002461:Cell Line, Transformed / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000473:pathology; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology; D002945:Cisplatin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D027383:Papillomaviridae; D010641:Phenotype; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin