
Topoisomerase I inhibitor suppress tumor growth in chemoresistant ovarian cancer-initiating cells
Author(s) -
Yu Chi Wang,
Chi-Ching Chang,
Kai Jo Chiang,
Tai-Kuang Chao,
Chia-Chun Wu,
Ping Chang,
Chang Chieh Wu,
Hung Cheng Lai
Publication year - 2014
Publication title -
yīxué yánjiū zázhì/journal of medical sciences
Language(s) - English
Resource type - Journals
eISSN - 2542-4939
pISSN - 1011-4564
DOI - 10.4103/1011-4564.131897
Subject(s) - ovarian cancer , topotecan , topoisomerase , cancer research , population , paclitaxel , cell culture , carboplatin , cancer , cisplatin , medicine , biology , in vitro , chemotherapy , genetics , environmental health
Background: To investigate the role of a topoisomerase I inhibitor (topotecan) in chemoresistant ovarian cancer-initiating cells. Materials and Methods: We isolated ovarian cancer-initiating cells (CP70 side-population cells) from the CP70 cell line using FACS Aria-based sorting and cultured them in suspension to form spheroids (CP70 side-population sphere [SPS]). Gene expression was assessed by microarray, to identify potentially effective chemotherapeutic drugs. An MTS assay was used to evaluate cell growth. Results: CP70 SPS cells showed significant resistance to the chemotherapeutic drugs cisplatin and paclitaxel. Microarray analysis demonstrated a high expression of topoisomerase-related genes in CP70 SPS cells. Topotecan inhibited ovarian cancer-initiating cells (CP70 SPS) in vitro more than it did their parental CP70 cells. This result was confirmed in tissues from human patients. Conclusions: Chemoresistant ovarian cancer-initiating cells exhibited high expression levels of topoisomerase, which could be an alternative target of adjuvant therapy for patients with chemoresistant ovarian cancer