Nodal Modulator Regulates Chemo- and Radioresistance in Lung Cancer via the Chk2 Pathway.

BACKGROUND/AIM: The limited efficacy of lung cancer treatment is partly due to the development of resistance to chemotherapy and radiotherapy. Recently, we identified Nodal modulators (NOMO1, NOMO2, and NOMO3), proteins involved in early embryonic patterning, as key factors in the radioresistance of lung cancer cells. Although NOMO proteins are highly expressed in lung cancer tissues, their roles in lung cancer have yet to be sufficiently determined.

MATERIALS AND

METHODS

To determine the function of NOMO, we assessed the effects of human NOMO-specific small interfering RNA (siRNA) on tumor cell viability and apoptosis.

RESULTS

NOMO silencing was found to counter the chemo- and radioresistance associated with caspase-dependent apoptosis in lung cancer cells. Furthermore, antibody array results revealed that the inhibition of NOMO leads to increased phosphorylation of the checkpoint kinases Chk1 and Chk2, which modulate chemo- and radioresistance.

CONCLUSION

NOMO and the Chk2 pathway are involved in chemo- and radioresistance in lung cancer, highlighting NOMO as a potential target for the development of gene therapies for the treatment of patients with lung cancer.