Effects Of E2F-1 On Proliferation, Apoptosis, Migration, Invasiveness And Chemosensitivity For Gastric Carcinoma

Gastric carcinoma is a common malignant tumor in our country, ranking the second cancer in male, and the third in female. Almost one third of the gastric carcinoma was at the late stage on diagnosis, lost the chance of surgical radication. Even those with surgical therapy, 60%-70% of the patients would have local recurrence and metastasis. However, chemotherapy, although as the main method, only have the response rate around 40%-50% in all the regimens. Thus, it is essential to seek any new method to increase the chemosensitivity. The transcription factor E2F-1 is essential for the control of cell circle and has the capability to induce apoptosis. Thus, E2F-1 gene can be a therapy target of cancer. In present study, we constructed the recombinant eukaryotic expression vector containing E2F-1 cDNA and harvested a stable gastric cancer cell line which over-expressed E2F-1. The effects of E2F-1 on proliferation, apoptosis, migration, invasiveness and chemosensitivity for gastric carcinoma in vitro were surveyed. To illustrate these changes, we investigated the differently expressive genes result from E2F-1 by cDNA microarray technique.Objective Investigate the effects and the mechanism of over-expression of E2F-1 gene on biological behaviors of gastric cancer cell line MGC803.Methods Constructed the eukaryotic expression vector pCMV-E2F-1-HA2, then stably transfected it into MGC-803 cell. After that, gathered genectin-resistant cell for function test in vitro. Cell cycle and apoptosis rate were examined by flow cytometry. MTT assay assessed proliferation rate and chemosensitivity. Cell matrigel invasion assay and scratching assay was used to assess the ability of migration and invasiveness for gastric carcinoma cells.Results Over-expression of E2F-1 gene results in G1 phase arrested in cell circle in gastric carcinoma cell. Over-expression of E2F-1 gene suppresses proliferation of gastric cancer and induces apoptosis. Over-expression of E2F-1 gene inhibits tumor cell invasion and migration and can improve chemotherapy sensitivity of tumor cells. The over-expressive E2F-1 resulted in 740 differentially expressed genes in gastric carcinoma.Conclusion 1.Over-expression of E2F-1 gene suppresses proliferation of gastric cancer and induces apoptosis. Over-expression of E2F-1 gene inhibits tumor cell invasion and migration and can improve chemotherapy sensitivity of tumor cells.2. E2F-1 resulted in 740 differentially expressed genes in gastric carcinoma cell, which might involve in so many pathways that distinguished biological behaviors occurred.