VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN

Yu,Xian; Xu,Zhengmin; Lei,Jun; Li,Tingting; Wang,Yan

doi:10.3892/mmr.2015.3509

July-2015 Volume 12 Issue 1

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July-2015 Volume 12 Issue 1

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Article

VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN

Authors:
- Xian Yu
- Zhengmin Xu
- Jun Lei
- Tingting Li
- Yan Wang
View Affiliations / Copyright

Affiliations: Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China, Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China
Pages: 1286-1290
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Published online on: March 18, 2015

https://doi.org/10.3892/mmr.2015.3509
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Abstract

PTEN acts as a phosphatidylinositol phosphatase with a possible role in the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway. Mutations in PTEN are frequent and their presence is associated with poor prognosis in breast cancer, which is the most common type of non‑cutaneous malignancy in females. Delivery of the tumor suppressor PTEN gene represents a powerful strategy for breast cancer therapy, but a present limitation of gene therapy is the ability to deliver sufficient quantities of active proteins to target cells. The capacity of HSV‑1VP22 fusion proteins to spread from the primary transduced cell to surrounding cells could improve gene therapeutics, particularly in cancer. To assess the potential efficacy of VP22 as a gene therapy for breast cancer, expression vectors for N‑ and C‑terminal PTEN‑VP22 fusion proteins were constructed. VP22‑mediated intercellular transport and antitumor efficacy in BT549 (PTEN‑null) breast tumor cells were investigated. The results showed that PTEN‑VP22 has the same spreading abilities as VP22. In cell proliferation and apoptosis assays, PTEN‑VP22 gene transfer induces a stronger anti‑proliferative effect and apoptotic activity compared with PTEN gene transfer alone. In addition, VP22 enhanced the PTEN‑mediated decrease in the level of phosphorylated AKT. The results show that PTEN‑VP22 can spread in vitro and PTEN‑VP22 gene induces significantly greater antitumor activity than the PTEN gene alone. This study confirms the utility of VP22‑mediated delivery in vitro and suggests that PTEN‑VP22 may have applications in breast cancer gene therapy.

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