1. Concomitant modulation of PTEN and Livin in gastric cancer treatment.
- Author
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Zhao CL, Han SN, Wang ZJ, Wang SH, Zhao GQ, Zhang XF, and Wang JX
- Subjects
- Animals, Apoptosis, Cell Line, Tumor, Gene Silencing, Genetic Therapy methods, Genetic Vectors genetics, Humans, Male, Mice, Inbred BALB C, Mice, Nude, Up-Regulation, Adaptor Proteins, Signal Transducing genetics, Gene Expression Regulation, Neoplastic, Genetic Vectors therapeutic use, Inhibitor of Apoptosis Proteins genetics, Neoplasm Proteins genetics, PTEN Phosphohydrolase genetics, Stomach Neoplasms genetics, Stomach Neoplasms therapy
- Abstract
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Livin are important in the development of gastric cancer (GC). PTEN and Livin are involved in the regulation of tumor cell proliferation, migration and apoptosis. The modulation of PTEN or Livin has been investigated extensively in various cancer models. However, no studies have been performed to evaluate the combined effect of concurrently modulating these two genes on the development of GC. In the present study, the BGC823 human gastric carcinoma cell line was transfected with a dual gene modified vector (pCL-neo-PTEN-siLivin) in parallel with single gene modified vectors (pCL‑neo‑PTEN or pRNAT‑U6.1‑siLivin), and an empty control vector. Dual gene modulation (pCL‑neo‑PTEN‑siLivin) had a more marked effect on the inhibition of cell proliferation, induction of apoptosis, and reduction of cell penetration in Matrigel, compared with either single gene alone or empty vector transfection. In a xenograft nude mouse model, the inoculation of pCL‑neo‑PTEN‑siLivin‑transfected BGC823 cells led to a markedly reduced tumor burden, compared with that in all other inoculation groups. In conclusion, the overexpression of PTEN concomitant with Livin gene silencing was confirmed as a feasible and effective in vitro and in vivo gene modulation method, which may represent a potential therapeutic strategy for the treatment of GC.
- Published
- 2018
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