Anti-cancer effects of n-3 long-chain polyunsaturated fatty acids (LCPUFA) on ovarian cancer growth in vitro and in vivo

• Author / Creator

  Hamedi, Bahareh

• Objectives: Many ovarian cancer (OC) patients relapse with chemo-resistant disease, necessitating improved therapeutic approaches. Recent studies have determined that long chain polyunsaturated fatty acids (LCPUFA) may affect cancer cell growth and metastatic potential; however, few studies have tested these in combination with chemotherapy in OC models. Herein, we investigated the effects of n-3 LCPUFAs on OC cell growth, and sensitivity to carboplatin, both in vitro and in vivo.

  Methods: In vitro, eight different OC cell lines were treated with different concentrations of fatty acids (0 to 320µM), alone and in combination with carboplatin, to assess the cytotoxicity.
  In vivo, mice transplanted with patient-derived xenograft (PDX) OC models were randomly assigned into four groups: basal diet (control), basal diet+carboplatin, docosahexaenoic acid diet (DHA, 3.8%), and DHA diet+carboplatin. Mice were fed with basal or DHA enriched diet for two weeks prior to weight-based treatment with carboplatin (40mg/kg every 3 days IP) and were kept on the same diet during chemotherapy.

  Results: In vitro, DHA alone inhibited proliferation of ES2 and A2780cp OC cells. Linear regression analysis demonstrated that DHA enhanced the cytotoxic effects of carboplatin on ES2, A2780cp, SKOV3, and Kuramochi cells. DHA reduced cell proliferation and induced cell cycle alteration in ES2 cells. In vivo, DHA enriched diet significantly reduced the tumor growth and increased the sensitivity of PDX tumors to carboplatin. Histological evaluation showed that the combination of DHA with carboplatin increased the area of necrosis and reduced the expression of Ki67 without induction of apoptosis.

  Conclusions: In vitro and in vivo evidence showed that DHA might increase the sensitivity of OC cells to platinum-based chemotherapy. Further studies, as well as clinical trials, are necessary to provide a strong rationale for a targeted n-3 LCPUFA intervention, as an adjuvant to the antineoplastic drug.

• Subjects / Keywords

  • ovarian cancer
  • n-3 long-chain polyunsaturated fatty acids
  • LCPUFA

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-44r2-2q82

• License

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