Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells

Abstract

The adoption of new treatment modalities is required to improve outcomes in lung cancer treatment as lung cancer has lowest survival rates, along with liver and pancreatic cancer. Bortezomib is a proteasome inhibitor that has higher anticancer effect in combination therapies. The aim of this study was to investigate whether bortezomib could have additional anticancer effect with antineoplastic tubulin binding agent -nocodazole in A549 lung cancer cells. Apoptosis related gene expression levels of Noxa, Bcl-xL, Casp3 and Casp7 were measured by real-time PCR after treatment with 30 nM bortezomib, 0.3 μg/ml nocodazole and with their combination for 24 hours. Synergistic effect on DNA damage response was investigated at protein levels by checking p53 and cleaved PARP expressions. Induction of apoptotis was determined at protein expression level by western blotting of XIAP, Bcl-X and Bim. It was found that nocodazole combined bortezomib treatment induced apoptosis via p53 mediated DNA damage response signalling. P53 and cleaved PARP protein expressions were increased significantly after combination treatment. Apoptosis related genes Noxa, Casp3 and Casp7 mRNA expressions were elevated significantly after combination treatment. This study concludes that bortezomib potentiates the effect of nocodazole via DNA damage induced apoptosis in A549 lung cancer cells.