TY - JOUR
T1 - RBPJ and MAML3
T2 - Potential therapeutic targets for small cell lung cancer
AU - Onishi, Hideya
AU - Ichimiya, Shu
AU - Yanai, Kosuke
AU - Umebayashi, Masayo
AU - Nakamura, Katsuya
AU - Yamasaki, Akio
AU - Imaizumi, Akira
AU - Nagai, Shuntaro
AU - Murahashi, Mutsunori
AU - Ogata, Hisanobu
AU - Morisaki, Takashi
N1 - Funding Information:
The Authors thank Ms. Emi Onishi for skillful technical assistance. This study was supported by JSPS KAKENHI Grant Number 17H04283 and 18K08788.
Publisher Copyright:
© 2018 International Institute of Anticancer Research. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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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U2 - 10.21873/anticanres.12758
DO - 10.21873/anticanres.12758
M3 - Article
C2 - 30061220
AN - SCOPUS:85050797895
SN - 0250-7005
VL - 38
SP - 4543
EP - 4547
JO - Anticancer research
JF - Anticancer research
IS - 8
ER -
