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Int J Gynaecol Obstet. 2019 May;145(2):225-232. doi: 10.1002/ijgo.12800. Epub 2019 Mar 15.

Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum.

Author information

1
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cooper University Hospital, Camden, NJ, USA.
2
Department of Surgery, Cooper University Hospital, Camden, NJ, USA.
3
Department of Surgical Research, Cooper University Hospital, Camden, NJ, USA.

Abstract

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 IC50 values of epigenetic drugs and paclitaxel and cisplatin were performed on Caov-3. Omental adipose-derived stem cells (OASCs) were isolated from omentum with/without metastases. Caov-3 was cultured with OASCs' 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 OASCs 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.

KEYWORDS:

Adipose-derived stem cells; Chemoresistance; Chemotherapy; Conditioned medium; Epigenetic drugs; Omental microenvironment; Omentum; Ovarian cancer; Secretome

PMID:
30828803
DOI:
10.1002/ijgo.12800

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