Colchicine sensitizes human hepatocellular carcinoma cells to damages caused by radiation.
OBJECTIVE
We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma (HCC) HA22T/VGH cells.


METHODS
Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses (0, 1, 2, 4, and 8 Gy). Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio (SER). Flow cytometry was used for cell cycle analysis.


RESULTS
Colchicine at lower concentrations (1 and 2 ng/mL) had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations (4 and 8 ng/mL) had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively. G(2)/M arrest was only observed with higher colchicine doses (8 and 16 ng/mL) after 24-h treatment; this effect was neither seen with lower doses (1, 2, and 4 ng/mL) nor with any dose after only 1 h of treatment.


CONCLUSIONS
Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment. Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G(2)/M arrest. Further study is necessary to elucidate the mechanism.
Liu
Chia-Yuan
CY
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 104, Taiwan, China.
Liao
Hui-Fen
HF
Shih
Shou-Chuan
SC
Lin
Shee-Chan
SC
Chang
Wen-Hsiung
WH
Chu
Cheng-Hsin
CH
Wang
Tsang-En
TE
Chen
Yu-Jen
YJ
D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003078:Colchicine / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms; D010315:Particle Accelerators; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D003078:Colchicine