Current Cancer Drug Targets

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


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.


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

Year: 2013
Page: [92 - 102]
Pages: 11
DOI: 10.2174/1568009611309010092