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Human papillomavirus type 16–immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype
Author(s) -
Ding Zhihu,
Yang Xiaolong,
Chernenko Garry,
Tang ShouChing,
Pater Alan
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000915)87:6<818::aid-ijc10>3.0.co;2-m
Subject(s) - multiple drug resistance , phenotype , virology , biology , cisplatin , human papillomavirus , cancer research , medicine , drug resistance , chemotherapy , microbiology and biotechnology , genetics , gene
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. Int. J. Cancer 87:818–823, 2000. © 2000 Wiley‐Liss, Inc.