title: Effects of gemcitabine on radiosensitization, apoptosis, and Bcl-2 and Bax protein expression in human pancreatic cancer xenografts in nude mice.
abstract: The aim of this study was to evaluate the radiosensitizing effects of gemcitabine towards human pancreatic cancer xenografts. A human pancreatic cancer xenograft model was established in nude mice, 36 of which were randomly divided into 6 treatment groups. Tumors were measured every 2 days, and the tumor volumes, growth delays, and inhibition rates were compared to evaluate the gemcitabine enhancement factor. The apoptotic index was determined by terminal deoxynucleotidyl transferase dUTP nick end-labeling assay, and apoptosis inhibitory protein Bcl-2 and apoptosis-related protein Bax expression were detected by immunohistochemistry. Compared with the control group, xenograft growth was significantly inhibited in the 25 (G25) and 50 mg/kg gemcitabine (G50) groups (P < 0.05). In the 25 (G25R) and 50 (G50R) mg/kg gemcitabine + radiotherapy groups, local tumor growth was significantly inhibited, with inhibition rates of 88.22 and 91.23%, respectively, significantly higher than those of the simple radiotherapy (SR), G25, and G50 groups (44.11, 72.88, and 77.53%, respectively; P < 0.05). The tumor growth delay in the G25R and G50R groups were 9 and 15 days, respectively, higher than the SR, G25, and G50 groups (each 4 days, P < 0.05). The apoptosis of tumor cells in the intervention groups significantly increased, and the apoptotic index among the intervention groups exhibited significant differences (P < 0.05). The immunohistochemical results indicated that Bcl-2 was downregulated to different degrees in the intervention groups, whereas Bax was upregulated (P < 0.05). Therefore, gemcitabine appears to enhance the radiotherapeutic sensitivity of human pancreatic cancer xenografts significantly.
authors.affiliation: Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Z T
authors.initials: ZT
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China xixuzhucn@163.com.
authors.forename: X X
authors.initials: XX
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003841:Deoxycytidine; D000093542:Gemcitabine