EfficientIn VitroTRAIL-Gene Delivery in Drug-Resistant A2780/DDP Ovarian Cancer Cell Line via Magnetofection

Fang Li,Donglu Shi,Huaishi Zhu,Yi Guo,Jing Sun,Qiujie Ba,Sumei Niu

doi:10.1155/2011/484589

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) presents great promise as an anticancer agent for human cancer therapy. In this study, a magnetofection agent (polyMAG-l000) was evaluated forin vitrodelivery of TRAIL gene towards drug-resistant A2780/DDP ovarian cancer cells. Transfection experiments showed that polyMAG-l000 was able to transfect A2780/DDP cellsin vitro, leading to a higher level of TRAIL gene expression in the presence of a static magnetic field as compared to other transfection agent, such as Lipofectamine 2000. TRAIL gene expression in the A2780/DDP cells was also confirmed by Western blot analysis. Moreover, the TRAIL gene expression exhibited remarkable decrease in the cell viability, as determined by MTT assay. Importantly, PolyMAG-l000-mediated TRAIL gene transfection in the presence of anticancer drug cisplatin (CDDP) induced much higher percentages of apoptotic A2780/DDP cells, compared to TRAIL gene transfection or CDDP treatment alone. A further study by Western blot analysis indicated that cytochromecrelease and caspase-9 cleavage pathway were associated with the initiation of the apoptosis in A2780/DDP cells. The results of this study indicate that polyMAG-l000 can be used as an efficient agent for TRAIL gene transfection in ovarian cancer cells.

Highlights

Ovarian carcinoma is the fifth most common gynaecological cancer
A further study by Western blot analysis indicated that cytochrome c release and caspase-9 cleavage pathway were associated with the initiation of the apoptosis in A2780/DDP cells
The results of this study indicate that polyMAG-l000 can be used as an efficient agent for Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene transfection in ovarian cancer cells

Summary

Introduction

Ovarian carcinoma is the fifth most common gynaecological cancer. Due to the lack of effective methods for early diagnosis of ovarian cancer, it is often detected in an advanced stage. Chemotherapy has to be discontinued due to intrinsic or developed drug resistance of the ovarian cancer cells. To address this critical issue, chemotherapy in combination with biological therapy has been studied in the past decade. Some recent studies indicated that a combined use of anticancer drugs with TNFrelated apoptosis-inducing ligand (TRAIL) protein had a synergistic effect on the apoptotic activity in ovarian cancer cells [2]

Methods

Results

Conclusion