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

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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