Establishment of primary human epithelial ovarian cancer cells and their application to cytotoxicity assessment

Abstract

Background: Ovarian carcinomas are highly metastatic tumors and the most lethal gynecological malignancies in the world. Treatment of human epithelial ovarian cancer (hEOC) is based on the combination of surgery and chemotherapy. The acquisition of resistance is a major obstacle to the clinical use of platinum drugs for 75% of high-grade serous ovarian cancer treatment. Hence, the urgent strategy is to develop platform to predict the resistance to targeted therapy after surgery and to screen the potential monotherapy, including platinum, in clinical treatment. Materials and Methods: Our laboratory tried to take advantage of ascites from hEOC patients to understand the mechanism of platinum-based resistance and screen the potential monotherapy choice via the primary culture strategy. We first established the culture conditions for ascites of the ovarian cancer patients. Results: We showed that we could culture these primary cells up to 13th generation. We further treated these primary cells with various steroid hormones for the epithelial-to-mesenchymal transient and regular monotherapy, including cisplatin, docetaxel, and doxorubicin, for the cytotoxicity. Finally, we also demonstrated the responsiveness of this monotherapy with antibodies against cell cycle, autophagy, or other survival-related factors. Conclusion: Our screening platform will provide us to further examine the resistance mechanism of any monotherapy in a different individual patient. We hope that our primary culture system used for standard monotherapy screening might provide the alert to drug resistance and the better combinatory therapy for personalized therapy.

Keywords

• human epithelial ovarian cancer
• cisplatin
• docetaxel
• doxorubicin
• drug resistance