title: Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.
abstract: Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Shanghui
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology*; D000099227:Abacavir
chemical_list: D015224:Dideoxynucleosides; D019259:Lamivudine; D011838:Radiation-Sensitizing Agents; D019098:Telomerase; D015215:Zidovudine; D000099227:Abacavir