TRAIL-secreting mesenchymal stem cells promote apoptosis in heat-shock-treated liver cancer cells and inhibit tumor growth in nude mice.
Liver cancer is one of the top six leading causes of cancer-related death. Radiofrequency ablation (RFA) is an important means of treating liver cancer. Residual cancer after RFA is the most frequent cause of recurrence in cases of liver cancer. The main difference between residual cancer cells and ordinary liver cancer cells is that residual cancer cells experience heat shock. The secretable form of trimeric human tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) induces apoptosis in a variety of human cancers but not in normal tissues. It has shown potent cancer-selective killing activity and has drawn considerable attention as a possible cancer therapy. In the present work, the therapeutic potential of this stTRAIL-based gene therapy was evaluated in hepatocellular carcinoma subjected to RFA. Rat bone marrow mesenchymal stem cells (BM-MSCs) were isolated and transduced with a lentiviral vector encoding stTRAIL (stTRAIL-MSCs, T-MSCs). Cells treated with heat treatment at 43 °C for 45 min served as simulated residual cancer cells. After treatment with T-MSCs, apoptosis in heat-shock-treated liver cancer cells increased significantly, and caspase-3 was upregulated. When T-MSCs were subcutaneously injected into nude mice, they localized to the tumors and inhibited tumor growth, significantly increasing survival. Collectively, the results of the present study indicate that BM-MSC can provide a steady source of stTRAIL and may be suitable for use in the prevention of the recurrence of hepatocellular carcinoma after RFA with secretable trimeric TRAIL.
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Deng
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Zhang
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Feng
1] Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China [2] Department of Hepatobiliary Surgery, Urumqi Military General Hospital, the Lanzhou Military Command, Urumqi, China.
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Li
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Liu
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Lai
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Shuai
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Xiong
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Fu
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Zou
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Wang
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Li
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Ma
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Bie
D000818:Animals; D017209:Apoptosis; D015316:Genetic Therapy; D056945:Hep G2 Cells; D006358:Hot Temperature; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand