Radiosensitivity of human colon cancer cell enhanced by immunoliposomal docetaxel.
OBJECTIVE
To enhance the radiosensitivity of human colon cancer cells by docetaxel.


METHODS
Immunoliposomal docetaxel was prepared by coupling monoclonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin.


RESULTS
Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoli-posomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dose-dependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation, strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation, immunoliposomal docetaxel significantly increased the percentage of G(2)/M cells and induced apoptosis, but significantly decreased the percentage of cells in G(2)/G(1) and S phase by comparison with liposomal docetaxel. Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells. Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased.


CONCLUSIONS
Immunoliposomal docetaxel is strongly effective for target radiosensitation in LoVo colon carcinoma cells, and may offer the potential to improve local radiotherapy.
Cancer Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China. wangqingwei@csco.org.cn
Qing-Wei
QW
Wang
Hui-Lan
HL
Lu
Chang-Cheng
CC
Song
Hong
H
Liu
Cong-Gao
CG
Xu
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003110:Colonic Neoplasms; D000077143:Docetaxel; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008081:Liposomes; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D043823:Taxoids / Q000633:toxicity*
D008081:Liposomes; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel