Matrine induces apoptosis via targeting CCR7 and enhances the effect of anticancer drugs in non-small cell lung cancer in vitro

Innate Immun. 2018 Oct;24(7):394-399. doi: 10.1177/1753425918800555. Epub 2018 Sep 20.

Abstract

This study mainly investigated the effects of matrine on cell apoptosis and the effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines (A549 and LK2 cells). The results showed that matrine (≥10 μM) caused a significant inhibition on cell viability and 10 and 100 μM matrine induced cell apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells. In addition, matrine significantly down-regulated C-C chemokine receptor type 7 (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of apoptosis genes in A549 cells. The results were further validated in LK2 cells that matrine regulated apoptosis gene expressions, which were reversed by CCL21 treatment. Furthermore, matrine enhances the effects of cisplatin, 5-fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibit a dosage-dependent manner. In summary, matrine induced cell apoptosis and enhanced the effects of anticancer drugs in NSCLC cells; the mechanism might be associated with the CCR7 signal.

Keywords: C-C chemokine receptor type 7; Matrine; apoptosis; non-small cell lung cancer.

MeSH terms

  • A549 Cells
  • Alkaloids / pharmacology*
  • Anthelmintics / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Chemokine CCL21 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Matrines
  • Quinolizines / pharmacology*
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Alkaloids
  • Anthelmintics
  • Antineoplastic Agents
  • CCR7 protein, human
  • Chemokine CCL21
  • Quinolizines
  • Receptors, CCR7
  • Tumor Suppressor Protein p53
  • Matrines