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Archive > Volume 21 Issue 3 > 2014,21(3):275-281. DOI:10.3872/j.issn.1007-385X.2014.03.007 Prev Next
Basic Research
Enhanced cytotoxicity of chemotherapeutic agents in combination with adenoviruses expressing MDA-7/IL-24 to esophageal carcinoma cells in vitro
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Abstract:
To evaluate the synergic antitumor effects of chemotherapeutic agents and melanoma differentiation-associated gene-7-expressing adenoviruses (Ad-MDA-7) in esophageal carcinoma cells in vitro. Methods: Human esophageal carcinoma TE-11 and YES-5 cells and human fibroblasts (control) underwent Ad-MDA-7 infection and chemotherapy, either each alone or in combination. Changes in mRNA levels of the IL-24 receptor complexes before and after treatment were assessed by RT-PCR. Cell viability was determined by MTT assays. Cell cycle progression was analyzed by flow cytometry. Results: Transcripts for IL-24 receptor complex components, IL-20R2, IL-20R1 and IL-22R1, were detected in both TE-11 and YES-5 cells but only IL-20R2 mRNA was detected in fibroblasts. TE-11 and YES-5 cells were susceptible were to Ad-MDA-7-mediated cytotoxicity in a dose-dependent manner; at 3×104 VP/cell, cytotoxicity was >80% and >50%, respectively, in TE-11 and YES 5 cells. In contrast, fibroblasts were resistant to Ad-mad-7. The cytotoxicity of 5-fluorouracil, cisplatin, mitomycin C or etoposide, each in combination with Ad-MDA-7 infection was significantly higher than that of these therapeutic agents and Ad-MDA-7, each alone. Increases in G2/M-phase and S-phase arrests were observed in cells, respectively, infected with Ad-MDA-7 and treated with 5-FU . The combination of Ad-mad-7 and 5-FU augmented sub-G1 populations. Compared with 5-FU alone, the combination regimen resulted in increases in caspase-8, -9, -3 expression and Akt phosphorylation and a decrease in IκB-α level. Conclusion: These data collectively suggest that adenovirus delivery of melanoma differentiation-associated gene-7 may enhance the sensitivity of esophageal carcinoma cells to chemotherapeutic agents through Akt activation.
Keywords:
esophageal carcinoma ; adenovirus ; MDA-7 ; IL-24 ; gene therapy ; chemotherapy
Project Supported:
Project supported by the Medical Scientific Research Key Plan of Hebei Province（No.20120125,No.20120128）
