Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis
Autor: | Emma Rodriguez, Guangsheng Pei, Zhongming Zhao, Sang Kim, Alexis German, Prema Robinson |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research cisplatin Inflammation Substance P Article 03 medical and health sciences 0302 clinical medicine Medicine MTT assay RC254-282 Aprepitant Triple-negative breast cancer Cisplatin business.industry Neurotoxicity Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology Oncology Apoptosis 030220 oncology & carcinogenesis triple negative breast cancer Cancer research medicine.symptom business Antagonism medicine.drug |
Zdroj: | Cancers Volume 13 Issue 15 Cancers, Vol 13, Iss 3871, p 3871 (2021) |
ISSN: | 2072-6694 |
Popis: | Simple Summary Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. In the current studies we determined a novel therapeutic option that enhances the efficacy of cisplatin and at the same time protects neuronal cells from cisplatin induced toxicity. Abstract Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. There is critically important to find new, effective and safe therapeutics for TNBC. We determined if SP-receptor antagonism in combination with cisplatin may serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. We used a neuronal cell line (PC12) and two TNBC cell lines (Sum 185 and Sum 159) for these studies. We determined that the levels of cells expressing the high-affinity SP-receptor (neurokinin 1 receptor (NK1R)), as determined by flow-cytometry was significantly elevated in response to cisplatin in all three cells. We determined that treatment with aprepitant, an SP-receptor antagonist decreased cisplatin-induced, loss of viability (studied by MTT assay), production of reactive oxygen species (by DCFDA assay) and apoptosis (by flow-cytometry) in PC12 cells while it was increased in the two TNBC cells. Furthermore, we demonstrated that important genes associated with metastases, inflammation, chemoresistance and cell cycle progression are attenuated by SP-receptor antagonism in the TNBC cell line, Sum 185. These studies implicate that SP-receptor antagonism in combination with cisplatin may possibly serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. |
Databáze: | OpenAIRE |
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