Human papillomavirus type 16-immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype

Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is a highly effective c hemotherapeutic agent against cervical cancer, but drug resistance is a maj or obstacle in its clinical application. The mechanism of drug resistance i n human cervical cancer is not well understood. Here, we established an in vitro endocervical, cisplatin-resistant cell system that mimics the develop ment of cisplatin resistance in the human cervix. Human papillomavirus (HPV ) type 16-immortalized human endocervical cells (HEN-16-2) were treated wit h cisplatin, and the cisplatin-selected cells (HEN-16-2/CDDP) were resistan t to cisplatin, paclitaxel, actinomycin D, doxorubicin, etoposide, and 5-fl uorouracil, thus demonstrating a multidrug resistance (MDR) phenotype, Furt hermore, 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 level s, higher saturation density, anchorage-independent growth, and formation o f tumors in nude mice, These results provided the first in vitro evidence t hat cisplatin selection can transform HPV-immortalized endocervical cells a nd cause a phenotype of MDR, Int. J. Cancer 87:818-823, 2000, (C) 2000 Wile y-Liss, Inc.