title: Oncolytic vaccine virus harbouring the IL-24 gene suppresses the growth of lung cancer by inducing apoptosis.
abstract: Lung cancer has an especially high incidence rate worldwide, and its resistance to cell death and chemotherapeutic drugs increases its intractability. The vaccinia virus has been shown to destroy neoplasm within a short time and disseminate rapidly and extensively as an enveloped virion throughout the circulatory system, and this virus has also demonstrated a strong ability to overexpress exogenous genes. Interleukin-24 (IL-24/mda-7) is an important cytokine that belongs to the activating caspase family and facilitates the inhibition of STAT3 when a cell enters the apoptosis pathway. In this study, we constructed a cancer-targeted vaccinia virus carrying the IL-24 gene knocked in the region of the viral thymidine kinase (TK) gene (VV-IL-24). Our results showed that VV-IL-24 efficiently infected and destroyed lung cancer cells via caspase-dependent apoptosis and decreased the expression of STAT3. In vivo, VV-IL-24 expressed IL-24 at a high level in the transplanted tumour, reduced STAT3 activity, and eventually led to apoptosis. In conclusion, we demonstrated that vv-IL-24 has the potential for use as a new human lung cancer treatment.
authors.affiliation: Xin Yuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China. Electronic address: lcw13284520839@126.com.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Lv
authors.affiliation: Xin Yuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China.
authors.forename: Qunshu
authors.initials: Q
authors.lastname: Su
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yupei
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Xin Yuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China.
authors.forename: Jinqing
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: yuansujing2013@sibcb.ac.cn.
authors.forename: Sujing
authors.initials: S
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D019496:Cancer Vaccines / Q000235:genetics* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics*; D000099180:Interleukin-24
chemical_list: D019496:Cancer Vaccines; D007378:Interleukins; D050796:STAT3 Transcription Factor; D000099180:Interleukin-24
keywords: Apoptosis; IL-24; Lung cancer; Oncolytic virus; Poxvirus