title: Experimental therapy for lung cancer: umbilical cord-derived mesenchymal stem cell-mediated interleukin-24 delivery.
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.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.forename: Shengqin
authors.initials: S
authors.lastname: Ye
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Hongcui
authors.initials: H
authors.lastname: Cao
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D036101:Cord Blood Stem Cell Transplantation; D005240:Feasibility Studies; D018014:Gene Transfer Techniques; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D055550:Protein Stability; D011994:Recombinant Proteins / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D051017:Apoptosis Regulatory Proteins; D007378:Interleukins; D011994:Recombinant Proteins; D000099180:Interleukin-24