Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Experimental Therapy for Lung Cancer: Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Interleukin-24 Delivery

Author(s): Xu Zhang, Leilei Zhang, Wenrong Xu, Hui Qian, Shengqin Ye, Wei Zhu, Hongcui Cao, Yongmin Yan, Wei Li, Mei Wang, Wei Wang, Ruiwen Zhang.

Abstract:

The use of adult stem cells as gene delivery vehicles is a novel and attractive strategy for cancer therapy. Mesenchymal stem cells (MSCs) provide a promising source for stem cell-based gene therapies. Interleukin-24 (IL24) has been suggested as an effective anticancer agent. However, a lack of tumor-targeted delivery and a host immune response to viral vehicles has hindered its application for cancer therapy. In this study, we evaluated the effects of IL24 delivered by MSCs as a therapeutic approach for lung cancer. We engineered human umbilical cord-derived MSCs (UC-MSCs) to efficiently deliver secretable IL24. We observed that IL24-transduced UC-MSCs (IL24-MSCs) inhibited the growth of A549 lung cancer cells by induction of apoptosis and cell cycle arrest. The IL24 proteins secreted by IL24-MSCs were involved in regulating the ERK-1/2, AKT and JNK signaling pathways. Additionally, MSCs-mediated IL24 expression led to an increase in the cleavage of caspases-3/8/9 and PARP, the Bax/Bcl-2 ratio, as well as the p21 expression in A549 cells. We also demonstrated that injection of IL24-MSCs significantly suppressed xenograft tumor growth. Moreover, the IL24-MSCs had anti-angiogenic effects both in vitro and in vivo. Taken together, our findings indicate that IL24 delivered by human UC-MSCs has the potential to be used as an alternative strategy for lung cancer therapy.

Keywords: Cancer therapy, interleukin-24, mesenchymal stem cells, targeted delivery

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Article Details

VOLUME: 13
ISSUE: 1
Year: 2013
Page: [92 - 102]
Pages: 11
DOI: 10.2174/1568009611309010092