GDC-0941 and CXCL8 (3-72) K11R/G31P combination therapy confers enhanced efficacy against breast cancer

Future Oncol. 2020 May;16(14):911-921. doi: 10.2217/fon-2020-0035. Epub 2020 Apr 14.

Abstract

Aim: Herein is presented the combined effect of PI3K inhibitor (GDC-0941) and CXCR1/2 analogue (G31P) in breast cancer. Materials & methods: Breast cancer cell lines and xenograft model were employed to test the efficacy of the combination therapy. Results: GDC-0941+G31P treatment substantially inhibited multiplication of all the breast cancer cell lines used in this study (BT474, HCC1954 and 4T1). Even though single therapies caused a meaningful S-phase cell cycle arrest, the inhibition effect was more potent with the combined treatment. Similarly, enhanced apoptosis accompanied GDC-0941+G31P treatment. Furthermore, the migration ability of the breast cancer cell lines were significantly curtailed by the combination therapy compared with the single treatments. Conclusion: The findings suggest that combination treatment involving PI3K inhibitor and CXCR1/2 analogue (G31P) could be a potent therapeutic option for breast cancer treatment.

Keywords: CXCR1/2; G31P; GDC-0941; PI3K; breast cancer; cancer immunology; cell cycle; combination therapy; metastasis; proliferation.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / drug effects
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Female
  • Humans
  • Indazoles / administration & dosage
  • Indazoles / pharmacology*
  • Interleukin-8 / administration & dosage
  • Interleukin-8 / pharmacology*
  • Mice
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors / administration & dosage
  • Receptors, Interleukin-8A / antagonists & inhibitors
  • Receptors, Interleukin-8B / antagonists & inhibitors
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • CXCL8(3-72)K11R,G31P, human
  • Indazoles
  • Interleukin-8
  • Peptide Fragments
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Sulfonamides