RBPJ and MAML3: Potential Therapeutic Targets for Small Cell Lung Cancer.

BACKGROUND/AIM: Small cell lung cancer (SCLC) is still a deadly type of cancer for which there are few effective therapeutic strategies. Development of a new molecule targeting agent is urgently desired. Previously we showed that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) are new therapeutic targets for pancreatic cancer. In the present study, we analyzed whether RBPJ/MAML3 inhibition could also be a new therapeutic strategy for SCLC.

MATERIALS AND METHODS: Using silencing of RBPJ/MAML3, proliferation, invasion, migration and chemosensitivity of SBC-5 cells were investigated.

RESULTS: RBPJ/MAML3 inhibition reduced Smoothened and HES1 expression, suggesting that RBPJ/MAML3 signaling was through Hedgehog and NOTCH pathways. In the analysis of cell functions, RBPJ/MAML3 inhibition significantly reduced proliferation and invasiveness via reduction of expression of matrix metalloproteinases. On the other hand, RBPJ/MAML3 inhibition also reduced chemosensitivity to cis-diamminedichlo-roplatinum and gemcitabine.

CONCLUSION: These results suggest that RBPJ and MAML3 could be new therapeutic targets for SCLC, however, chemosensitivity may be reduced in combinational use with other chemo-therapeutic agents.