Evaluation of the Effect of Resveratrol and Doxorubicin on 99mTc-MIBI Uptake in Breast Cancer Cell Xenografts in Mice

Cancer Biother Radiopharm. 2018 Nov;33(9):403-410. doi: 10.1089/cbr.2018.2523. Epub 2018 Jul 24.

Abstract

Background and objective: Doxorubicin (DOX), despite having antitumor properties, also exhibits cardiotoxicity. Resveratrol has antitumor property for breast cancer cells. 99mTc-MIBI has higher absorption rate in human breast cancer cell line MCF-7. In the present study, the authors intend to investigate the effect of DOX and resveratrol on the absorption of 99mTc-MIBI in breast cancer cell xenografts in mice.

Materials and methods: Sixteen xenograft models in nude mice were divided into four groups. Group I (S, control) received 2% DMSO in 0.9% saline, group II (D) 2.5 mg/kg DOX, group III (D + R) 20 mg/kg/d resveratrol with 2.5 mg/kg DOX (total dose of 15 mg/kg in six injections), and group IV (R) 20 mg/kg/d resveratrol for 2 weeks. Single-photon emission computed tomography (SPECT) images were taken for the determination of 99mTc-MIBI absorption. Mice were sacrificed, and the percentage of injected dose per gram (%ID/g) of the heart, liver, tumor, and muscle was measured using a gamma counter. Hematoxylin-eosin staining and Masson's trichrome staining were used for investigation of histopathological changes.

Results: The %ID/g of tumor was lowest in group D + R. The severity of tumor necrosis or apoptosis was highest in group D + R, but there is no significant difference in pathological injuries and %ID/g of tumor between the group D + R and group D. In addition to the results of the %ID/g, the severity of pathological injuries to the liver and heart cells in group D + R was higher compared with group D. There is a significant difference in the %ID/g of the liver between the group D + R and group D. SPECT images showed that the lowest amount of %ID/g was observed in the tumor of group D + R.

Conclusions: According to the results of pathology, biodistribution study, and imaging, the combination of DOX and resveratrol has shown higher antitumor effect; hence, 99mTc-MIBI can be used to evaluate their antitumor effect.

Keywords: 99mTc-MIBI; breast cancer; doxorubicin; resveratrol.

MeSH terms

  • Animals
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Doxorubicin / pharmacokinetics*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Resveratrol / pharmacology*
  • Technetium Tc 99m Sestamibi / pharmacokinetics*
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Doxorubicin
  • Technetium Tc 99m Sestamibi
  • Resveratrol