Novel Synergistic Combination of Pamidronate and Temozolomide for Breast Cancer Therapeutics

Autor: Nida, Syed, Amber, Ilyas, Basir, Syed, Aftab, Ahmed, Shamshad, Zarina, Zehra, Hashim
Rok vydání: 2023
Předmět:
Zdroj: Current Cancer Drug Targets. 23:222-234
ISSN: 1568-0096
DOI: 10.2174/1568009622666220921103201
Popis: Objective: Human breast cancer is among one major health concerns with high prevalence and mortality among women worldwide. Various cellular signaling pathways are implicated in carcinogenesis. One of the major pathways that affect the downstream cellular growth cascades is Mevalonate pathway (MVA). The inhibition of MVA is therapeutically beneficial for various cancers. Pamidronate (PAM) (MVA inhibitor), a nitrogen-containing bisphosphosphonate, is an antiresorptive FDAapproved drug. The objective of our study was to explore adjuvant therapy using a combination of PAM and an alkylating agent, Temozolomide (TMZ) against breast cancer. Methods: We have examined the differential gene and protein expression in response to the combination treatment strategy. For gene expression analysis RT-qPCR and for proteomic study, twodimensional gel electrophoresis and mass spectrometry techniques were utilized. Results: Combination treatment (PAM+TMZ) showed more pronounced cytotoxic effect as compared to single agent treatment. Our results indicate that MVA pathway regulatory genes (FDFT1, FDPS, KRAS) are significantly (p Conclusion: The present study reveals that a combination of PAM and TMZ produces an effective anti-cancerous effect on breast cancer cells. Therefore, this novel therapeutic regimen is likely to provide a better treatment strategy for breast cancer.
Databáze: OpenAIRE