Low-dose irradiation and short-exposure suboptimal-dose paclitaxel adversely modulate metastatic potential of squamous carcinoma cells.
OBJECTIVE
Low-dose irradiation and suboptimal drug concentrations may induce unexpected biological responses. Paclitaxel (PTX) is a widely used drug, which has a range of antitumoral effects and which is also regarded as a radiation sensitizer. In this study, it was tested how "suboptimal" short exposure to PTX modifies the biological effects of low-dose irradiation on human epithelial carcinoma cell lines.


METHODS
2 Gy irradiation, 7 and 100 nM PTX treatment, and their combinations were tested on squamous and transitional cell carcinoma lines A431, KB and ECV304. Cytoskeleton of interphase cells was investigated with immunocytochemistry and confocal laser scanning microscopy; viability and clonogenicity were assessed with MTT test and standard clonogenic assay. Effects on tumor growth and metastatic potential of A431 cells were tested in vivo using a liver metastasis model in SCID mice.


RESULTS
Exposure of human tumor cells to irradiation induced bundling of microtubules, similar to PTX. Combined treatments suspended each other's effect independently of treatment combinations. Single or combination treatments with low-dose PTX did affect cell proliferation to no relevant extent in vitro or in vivo (primary tumor xenografts of A431 cells). However, exposure to irradiation of A431 cells inhibited while 100 nM PTX stimulated their liver-metastatic potential. Combination of 100 nM PTX with irradiation suspended the effect of 100 nM PTX and exhibited the highest antimetastatic activity.


CONCLUSIONS
Short exposure to PTX and irradiation can interfere with each other's effects on tumor cells without significant modulation of proliferation and tumorigenicity. However, PTX and irradiation may significantly modulate the metastatic property of tumor cells.
Lövey
József
J
Department of Radiotherapy, National Institute of Oncology, Budapest, Hungary.
Fazekas
Károly
K
Ladányi
Andrea
A
Németh
György
G
Tímár
József
J
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D003599:Cytoskeleton; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007399:Interphase; D008113:Liver Neoplasms / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D009362:Neoplasm Metastasis / Q000503:physiopathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011879:Radiotherapy Dosage
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel