Abstract
Background: Over expression of ATP-binding cassette (ABC) transporter protein (ABCG2) in side
population cells plays a crucial role in the chemotherapeutic drug efflux. Constitutive
expression of redox sensing transcritption factor Nrf2 was shown to be involved in
regulation of ABCG2 expression and chemoresistance. In the current study we made an
attempt to characterize the lung adenocarcinoma SP cells.
Materials and Methods: We used FACs based Hoechst 33342 dye exclusion assay for purification of lung cancer
SP cells. The sorted SP cells were subjected to drug resistance, sphere formation
assays and gene expression analysis (Nrf2 and ABCG2).
Results: We have identified 2.9% of SP cells from lung cancer whose prevalence is significantly
reduced to 0.3% upon treatment with verapamil. RT-PCR and western blot analysis revealed
that Nrf2 and ABCG2 were highly expressed in lung cancer SP cells. Further, these
SP cells are resistant to several chemotherapeutic drugs, self-renewal, and highly
tumorigenic than non-SP cells.
Conclusions: Our data suggest that Nrf2-mediated ABCG2 over expression in lung adenocarcinoma
SP cells might responsible for chemotherapy failure. Therefore, designing novel anticancer
drugs that attenuates the Nrf2 and ABCG2 expression, makes SP cells more sensitive
to chemotherapy and thus prevent the tumor relapse.
Key words
cancer stem-like cells - side-population cells - self-renewal - Nrf2 - chemoresistance