[Cytotoxicity of pentoxifylline and its effect on human hepatoma cell line Hep3b radiosensitivity].
OBJECTIVE
To investigate the effects of pentoxifylline (PTX) on radiation induced-cell cycle redistribution and radiosensitivity of human hepatocellular carcinoma cell line Hep3b.


METHODS
MTT assay was performed to evaluate the cytotoxicity of PTX on p53-defective human hepatocellular carcinoma cell line Hep3b and clonogenic assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). Flow cytometry was performed to observe the cell cycle changes of Hep3b cells in response to X-ray irradiation and the interventional effect of PTX.


RESULTS
The cytotoxicity of PTX on the cells increased in a dose-dependent manner following a 48-hour treatment, with the optimal dose range of 1-5 mmol/L. A sub-toxic dose of PTX at 2 mmol/L was then used in subsequent experiments. Clonogenic survival assays up to 12 Gy demonstrated that p53-defective Hep3b cells (SER of 2.68+/-0.24) were sensitized by PTX (2 mmol/L). PTX (2 mmol/L) treatment following exposure to irradiation (6 Gy) resulted in abrogation of radiation-induced G(2)/M arrest of Hep3b cells, and the proportions of Hep3b cells in G(2)/M phase were 86.8% and 14.8% after exposure to 6 Gy alone and 6 Gy plus 2 mmol/L PTX, respectively.


CONCLUSIONS
Radiosensitization by PTX is possibly associated with the abrogation of G(2)/M arrest in Hep3b cells following radiation exposure, suggesting that potential clinical application of PTX may enhance the efficacy of radiotherapy against hepatocellular carcinoma.
Wu
De-hua
DH
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Liu
Li
L
Chen
Long-hua
LH
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D010431:Pentoxifylline / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014965:X-Rays
D011838:Radiation-Sensitizing Agents; D010431:Pentoxifylline