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
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Animals
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Apoptosis / drug effects
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Breast Neoplasms / diagnosis
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism
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Breast Neoplasms / mortality
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Cell Cycle / drug effects
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Cell Cycle Checkpoints / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Disease Models, Animal
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Female
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Humans
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Indazoles / administration & dosage
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Indazoles / pharmacology*
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Interleukin-8 / administration & dosage
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Interleukin-8 / pharmacology*
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Mice
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Peptide Fragments / administration & dosage
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Peptide Fragments / pharmacology*
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Phosphoinositide-3 Kinase Inhibitors / administration & dosage
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Receptors, Interleukin-8A / antagonists & inhibitors
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Receptors, Interleukin-8B / antagonists & inhibitors
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Sulfonamides / administration & dosage
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Sulfonamides / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
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CXCL8(3-72)K11R,G31P, human
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Indazoles
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Interleukin-8
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Peptide Fragments
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Phosphoinositide-3 Kinase Inhibitors
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Receptors, Interleukin-8A
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Receptors, Interleukin-8B
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Sulfonamides