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Journal of Cancer Research and Clinical Oncology

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01.06.2014 | Original article – Cancer Research

Synergistic effects of eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes on lung cancer in vitro and in vivo

verfasst von: Lingdong Li, Chuanjiang Yu, Jiang Ren, Sujuan Ye, Wenjing Ou, Yu Wang, Weihan Yang, Guoxing Zhong, Xiang Chen, Huashan Shi, Xiaolan Su, Lijuan Chen, Wen Zhu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2014

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Abstract

Purpose

LKB1 and FUS1 are two kinds of new tumor suppressor genes as well as early-stage genes in lung cancer. Recent studies showed that LKB1 and FUS1 play important roles in lung carcinogenesis process. We hypothesized that combined gene therapy with LKB1 and FUS1 could inhibit lung cancer growth and development synergistically.

Methods

In this study, two kinds of tumor suppressor genes, LKB1 and FUS1, were constructed in an eukaryotic coexpression plasmid pVITRO₂, and then, we evaluated the synergistic effects of the two genes on anticancer activity and explored the relevant molecular mechanisms.

Results

We defined coexpression of LKB1 and FUS1 could synergistically inhibited lung cancer cells growth, invasion and migration and induced the cell apoptosis and arrested cell cycle in vitro. Intratumoral administration of liposomes: pVITRO₂–LKB1–FUS1 complex (LPs–pVITRO₂–LKB1–FUS1) into subcutaneous lung tumor xenograft resulted in more significant inhibition of tumor growth. Furthermore, intravenous injection of LPs–pVITRO₂–LKB1–FUS1 into mice bearing experimental A549 lung metastasis demonstrated synergistic decrease in the number of metastatic tumor nodules. Finally, combined treatment with LKB1 and FUS1 prolonged overall survival in lung tumor-bearing mice. Further study showed that the synergistic anti-lung cancer effects of coexpression of LKB1 and FUS1 might be related to upregulation of p-p53, p-AMPK and downregulation of p-mTOR, p-FAK, MMPs, NEDD9, VEGF/R and PDGF/R.

Conclusions

Our results suggest that combined therapy with eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes may be a novel and efficient treatment strategy for human lung cancer.

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Titel: Synergistic effects of eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes on lung cancer in vitro and in vivo
verfasst von: Lingdong Li
Chuanjiang Yu
Jiang Ren
Sujuan Ye
Wenjing Ou
Yu Wang
Weihan Yang
Guoxing Zhong
Xiang Chen
Huashan Shi
Xiaolan Su
Lijuan Chen
Wen Zhu
Publikationsdatum: 01.06.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2014
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1607-5

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Synergistic effects of eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes on lung cancer in vitro and in vivo

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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