Journal of Medical Sciences (Jan 2014)

Topoisomerase I inhibitor suppress tumor growth in chemoresistant ovarian cancer-initiating cells

  • Yu-Chi Wang,
  • Cheng-Chang Chang,
  • Kai-Jo Chiang,
  • Tai-Kuang Chao,
  • Chia-Chun Wu,
  • Ping-Ying Chang,
  • Chang-Chieh Wu,
  • Hung-Cheng Lai

DOI
https://doi.org/10.4103/1011-4564.131897
Journal volume & issue
Vol. 34, no. 2
pp. 72 – 76

Abstract

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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.

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