Docetaxel shows radiosensitization in human hepatocellular carcinoma cells.
OBJECTIVE
To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.


METHODS
SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time.


RESULTS
The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h.


CONCLUSIONS
A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.
Geng
Chang-Xin
CX
Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China. changxin_geng@hotmail.com
Zeng
Zhao-Chong
ZC
Wang
Ji-Yao
JY
Xuan
Shi-Ying
SY
Lin
Chong-Mao
CM
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D000077143:Docetaxel; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D010084:Oxidation-Reduction; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D043823:Taxoids; D000077143:Docetaxel