Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells

• Published in: BMC research notes 2017-11, Vol.10 (1), p.544-544, Article 544
• Main Authors: Sooman, Linda, Gullbo, Joachim, Bergqvist, Michael, Bergström, Stefan, Lennartsson, Johan, Ekman, Simon
• Format: Article
• Language: English
• Subjects: Analysis; Bortezomib; Cancer therapies; Chemoresistance; Chemotherapy; Cisplatin; Combination chemotherapy; Combination drug therapy; Complications and side effects; Cytotoxicity; Diagnosis; Dosage and administration; Drug therapy; Epidermal growth factor; Gefitinib; Gemcitabine; Kinases; Lung cancer; Lymphoma; Medical prognosis; Medicin och hälsovetenskap; Multiple myeloma; Mutation; Patients; Prognosis; Proteasome inhibitors; Proteins; Tumor cell lines; Vinorelbine
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-017-2842-z

The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients. The median-effect method was applied to the Fluorometric Microculture Cytotoxicity Assay (FMCA) to evaluate effects of combining two different PIs (bortezomib and b-AP15) with clinically used chemotherapeutic drugs representing different mechanisms of action (cisplatin, gefitinib, gemcitabine and vinorelbine) in two lung cancer cell lines (one sensitive and one resistant). Proteasome inhibition in combination with cisplatin, gemcitabine or vinorelbine had synergistic effects in at least one of the tested cell lines. Furthermore, the effect of gefitinib appeared strongly potentiated by the PI in the least resistant lung cancer cell line, although the level of synergy could not be determined with the median-effect method. Combining PIs with cisplatin, gefitinib, gemcitabine or vinorelbine show potential as new combination chemotherapy for the treatment of lung cancer.