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Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum
Author(s) -
Sookram Janhvi,
Zheng Andrew,
Linden Kimberly M.,
Morgan Andrew B.,
Brown Spencer A.,
Ostrovsky Olga
Publication year - 2019
Publication title -
international journal of gynecology and obstetrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.895
H-Index - 97
eISSN - 1879-3479
pISSN - 0020-7292
DOI - 10.1002/ijgo.12800
Subject(s) - medicine , ovarian cancer , epigenetics , cisplatin , paclitaxel , epigenetic therapy , cytotoxicity , chemotherapy , cancer research , oncology , mtt assay , cancer , pharmacology , cell , dna methylation , biology , in vitro , genetics , biochemistry , gene expression , gene
Objective To examine the cytotoxicity of epigenetic drugs independently and in combination with chemotherapy on ovarian cancer cells Caov‐3, and to investigate their ability to acquire chemoresistance in omental microenvironments and whether epigenetic drugs can counteract this chemoresistance. Methods A pilot study was conducted in Cooper University Hospital, NJ , USA from August 1 to October 31, 2017, among women undergoing surgeries for uterine and ovarian cancer. Cytotoxicity assays using IC 50 values of epigenetic drugs and paclitaxel and cisplatin were performed on Caov‐3. Omental adipose‐derived stem cells ( OASC s) were isolated from omentum with/without metastases. Caov‐3 was cultured with OASC s’ conditioned medium and subjected to different drugs. Cell viability and secretome was measured using MTT and Elisa, respectively. Results Three women met the eligibility criteria and were included in the study. Epigenetic drugs alone or in combination with chemotherapy showed 85%–94% increased cytotoxicity against Caov‐3 ( P ≤0.005). Metastatic OASC s conditioned medium showed up to 27‐fold increase in tumorigenic factors and promoted chemoresistance (28%–35%; P < 0.050) against chemotherapy. Epigenetic therapy resulted in up to a 40‐fold reversal in this chemoresistance. Conclusion Epigenetic therapies could have an important role in treating a subgroup of ovarian cancer patients that demonstrate resistance to first‐line chemotherapy.