In vitro and in vivo effect of flutamide on steroid hormone secretion in canine and human inflammatory breast cancer cell lines

Vet Comp Oncol. 2018 Mar;16(1):148-158. doi: 10.1111/vco.12324. Epub 2017 Jun 6.

Abstract

The aim was to study the effects of flutamide on cell proliferation, in vivo tumour growth and steroid production in canine and human IBC cell lines. IPC-366 and SUM149 cell cultures were exposed to flutamide concentrations for 72 hours. Additionally, IPC-366 and SUM149 xenotransplanted mice were treated subcutaneously with flutamide 3 times a week for 2 weeks. Steroid hormones determination in culture media, serum and tumour homogenates (pregnenolone, progesterone, androstenedione, testosterone, dihydrotestosterone, 17β-oestradiol and oestrone sulphate) were assayed by EIA. in vitro cell proliferation percentages showed a decrease in all flutamide dosages in IPC-366 and SUM149. in vivo flutamide reduced tumour size by 55% to 65%, and metastasis rates decreased. In treated groups, androgen levels in culture media, serum and tumour homogenates were increased as oestrogen levels decreased. These results suggest that flutamide treatment inhibits cell proliferation and promotes tumour reduction by increasing androgen levels and also support future therapy approaches.

Keywords: IBC; IMC; flutamide; steroid hormones; tumour growth.

MeSH terms

  • Androstenedione / metabolism
  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Dihydrotestosterone / metabolism
  • Dog Diseases / drug therapy*
  • Dogs
  • Estradiol / metabolism
  • Estrone / analogs & derivatives
  • Estrone / metabolism
  • Female
  • Flutamide / therapeutic use*
  • Gonadal Steroid Hormones / metabolism*
  • Humans
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Pregnenolone / metabolism
  • Progesterone / metabolism
  • Testosterone / metabolism

Substances

  • Antineoplastic Agents, Hormonal
  • Gonadal Steroid Hormones
  • Dihydrotestosterone
  • Estrone
  • Testosterone
  • Androstenedione
  • Progesterone
  • Estradiol
  • Pregnenolone
  • Flutamide
  • estrone sulfate