Matrine reversed multidrug resistance of breast cancer MCF-7/ADR cells through PI3K/AKT signaling pathway

J Cell Biochem. 2018 May;119(5):3885-3891. doi: 10.1002/jcb.26502. Epub 2018 Jan 22.

Abstract

Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, and has been used clinically for breast cancer with marked therapeutic efficacy in China. However, the mechanism has not been well known. Thus, the present study was to explore whether Matrine reverses multidrug resistance for breast cancer cells through the regulation of PI3K/AKT signaling pathway. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the inhibitory action; Annexin V to detect apoptosis; fluorospectrophotometry to examine intracellular adriamycin (ADR) accumulation; and Western blot to label the proteins of P-glycoprotein (P-gp), MRP1, PTEN, p-AKT, Bcl-2, Bax, and Caspase-3. Matrine (0-2.5 mg/mL) inhibited MCF-7/ADR cell growth and induced apoptosis (P < 0.01). A total of 0.2 mg/mL Matrine could increase the intracellular concentration of ADR; the accumulation in MCF-7/ADR cells increased 3.56 times. Compared with control group, 0.6, 1.2 mg/mL Matrine reduced protein expressions of P-gp, MRP1, p-AKT, Bcl-2, but increased PTEN, Bax, and cleaved caspase-3 gradually, and unchanged caspase-3. Matrine was more likely to reduce the expression of P-gp, MRP1, and p-AKT at the same inhibition radio of Matrine, (0.6 mg/mL) and MK2206 (0.05 μmol/L). Matrine inhibited MCF-7/ADR cell growth, induced apoptosis, and reversed multidrug resistance for breast cancer cells through the regulation of downstream apoptosis factors of PI3K/AKT signaling pathway by decreasing cell phosphorylation of AKT level.

Keywords: MCF-7/ADR; Matrine; PI3 K/AKT signal pathway; multidrug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • MCF-7 Cells
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Quinolizines / pharmacology*

Substances

  • Alkaloids
  • Quinolizines
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • matrine