title: Caffeine enhances radiosensitization to orthotopic transplant LM3 hepatocellular carcinoma in vivo.
abstract: The aim of this study was to determine whether caffeine enhanced radiosensitization in an orthotopic transplant of LM3 human hepatocellular cancer in nude mice. LM3 hepatocellular carcinoma cells were infected with red fluorescent protein and irradiated, and cell cycle distribution and survival fraction were detected. A nude mouse model of orthotopic transplant of red fluorescent protein-expressing LM3 hepatocellular cancer was established. Nude mice were divided into four groups: control (NS); caffeine (Caff) alone; irradiation (IR) alone; and caffeine + IR (Caff + IR). Tumor growth curves were described. Expression of cyclin and apoptosis were evaluated by analysis of phosphorylated cyclin dependent kinase 1 (CDC2) Tyr15 (CDC2-Tyr15-P), cyclinB1, TUNEL staining, and caspase-3. Caffeine abrogated IR-induced G(2) phase arrest and decreased survival of irradiated LM3 cells. Caffeine enhanced radiosensitivity of LM3 hepatocellular cancer in vivo. Tumor growth delay time in the Caff + IR group was 14.3 days compared with the NS group, 14.1 days compared with the Caff alone group, and 7.2 days compared with the IR alone group. At 15 Gy, expression of CDC2-Tyr15-P in the Caff + IR group (26.0 +/- 8.9%) was significantly lower than in the IR alone group (68.4 +/- 10.6%), expression of cyclinB1 and proportion of TUNEL-positive cells in the Caff + IR group (30.4 +/- 8.7% and 59.2 +/- 9.5%, respectively) was significantly higher than in the IR alone group (7.0 +/- 3.7% and 24.2 +/- 7.2%, respectively), expression of caspase-3 was consistent with the TUNEL staining results. This study suggested that caffeine might enhance the radiosensitivity of LM3 hepatocellular cancer in vivo, and may be feasible for further clinical applications.
authors.affiliation: Department of Radiation Oncology, the Second Affiliated Hospital of Jilin University, Changchun, China.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Wang
authors.forename: Zhong-Shan
authors.initials: ZS
authors.lastname: Liu
authors.forename: Zhao-Chong
authors.initials: ZC
authors.lastname: Zeng
authors.forename: Shi-Suo
authors.initials: SS
authors.lastname: Du
authors.forename: Ming
authors.initials: M
authors.lastname: Qiang
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Zhang
authors.forename: Zheng-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wu
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000032:analysis; D016195:G2 Phase / Q000528:radiation effects; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011836:Radiation Tolerance / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D016159:Tumor Suppressor Protein p53; D002110:Caffeine; D016203:CDC2 Protein Kinase
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