Tsai, HE and Liu, LF and Dusting, GJ and Weng, WT and Chen, SC and Kung, ML and Tee, R and Liu, GS and Tai, MH, Pro-opiomelanocortin gene delivery suppresses the growth of established Lewis lung carcinoma through a melanocortin-1 receptor-independent pathway, Journal of Gene Medicine, 14, (1) pp. 44-53. ISSN 1099-498X (2012) [Refereed Article]
Copyright 2012 John Wiley & Sons, Ltd.
Methods: In the present study, the therapeutic efficacy of POMC gene therapy was evaluated in mice bearing established Lewis lung carcinoma (LLC) models both in vitro and in vivo. We also investigated the MC-1R-independent mechanism underlying POMC gene therapy.
Results: We found that POMC gene delivery significantly inhibited the growth and colony formation in MC-1R-deficient LLC cells. In addition, POMC gene transfer effectively suppressed the growth of established LLC in mice. The inhibitory mechanisms underlying POMC gene delivery were attibuted to be inhibition of proliferation and the induction of apoptosis. Moreover, POMC gene delivery attenuated tumor β-catenin signaling by reducing protein levels of β-catenin and its downstream proto-oncogenes, including cyclin D1 and c-myc. Lastly, POMC gene delivery induced a significant suppression of tumor vasculature.
Conclusions: These results support the existence of an MC-1R-independent pathway for POMC gene therapy, which further expands the therapeutic spectrum of POMC therapy for multiple types of cancer.
|Item Type:||Refereed Article|
|Keywords:||POMC, MC1R, b-catenin, gene therapy, lung cancer|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Medical biotechnology|
|Research Field:||Gene and molecular therapy|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Liu, GS (Associate Professor Guei-Sheung Liu)|
|Web of Science® Times Cited:||19|
|Deposited By:||Menzies Institute for Medical Research|
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