Journal
ANTICANCER RESEARCH
Volume 38, Issue 8, Pages 4543-4547Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.12758
Keywords
RBPJ; MAML3; SCLC; therapeutic target
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Funding
- JSPS KAKENHI [17H04283, 18K08788]
- Grants-in-Aid for Scientific Research [17H04283, 18K08788] Funding Source: KAKEN
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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 mastermindlike 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.
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