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Published on: January 19, 2019
Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer
Yaru Zhao1,2, Huihui Liu1, Qi Zhan1
1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
Abstract:
LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.
Insights
A novel oncolytic adenovirus, GD55-LHPP, effectively targets lung cancer by restoring the tumor suppressor LHPP. This therapy inhibits cancer cell growth, induces apoptosis, and improves survival rates in preclinical models.
Area of Science:
- Oncology
- Gene Therapy
- Virology
Background:
- LHPP functions as a tumor suppressor and is often underexpressed in various cancers.
- Oncolytic virotherapy has emerged as a promising therapeutic strategy for lung cancer.
Purpose of the Study:
- To construct and evaluate a novel recombinant oncolytic adenovirus, GD55-LHPP, for lung cancer therapy.
- To investigate the effects of GD55-LHPP on lung cancer cell growth, apoptosis, and autophagy both in vitro and in vivo.
Main Methods:
- Construction of the recombinant oncolytic adenovirus GD55-LHPP.
- Assessment of LHPP expression in lung cancer cells and tissues.
- In vitro studies on lung cancer cell proliferation and apoptosis.
- In vivo studies using lung cancer xenograft mouse models.
Main Results:
- LHPP expression was significantly lower in lung cancer cells and tissues compared to normal counterparts.
- GD55-LHPP effectively mediated LHPP expression in lung cancer cells, inhibiting their proliferation while sparing normal cells.
- GD55-LHPP induced stronger apoptosis in lung cancer cells via caspase pathway activation and also activated autophagy.
- GD55-LHPP significantly inhibited tumor growth in mice and improved survival rates.
Conclusions:
- The novel construct GD55-LHPP offers a promising strategy for targeted lung cancer therapy.
- This approach leverages the tumor-suppressive role of LHPP in gene therapy for lung cancer.
