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:10.4103/1011-4564.131897

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ORIGINAL ARTICLE

Year : 2014 | Volume : 34 | Issue : 2 | Page : 72-76

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

Yu-Chi Wang¹, Cheng-Chang Chang¹, Kai-Jo Chiang², Tai-Kuang Chao³, Chia-Chun Wu⁴, Ping-Ying Chang⁵, Chang-Chieh Wu⁶, Hung-Cheng Lai⁷
¹ Department of Obstetrics and Gynecology, Tri-Service General Hospital; Laboratory of Epigenetics and Cancer Stem Cells, National Defense Medical Center, Taipei, Taiwan, Republic of China
² Department of Nursing, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
³ Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
⁴ Department of Orthopedic, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
⁵ Department of Internal Medicine, Division of Hematology and Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
⁶ Department of Surgery, Division of Colorectal Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
⁷ Department of Obstetrics and Gynecology, Tri-Service General Hospital; Laboratory of Epigenetics and Cancer Stem Cells, National Defense Medical Center; Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, Zhonghe District, New Taipei City, Taiwan, Republic of China

Correspondence Address:
Prof. Hung-Cheng Lai
Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City 235, Taiwan
Republic of China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1011-4564.131897

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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