Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice.
OBJECTIVE
To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy and thermochemoradiotherapy.


METHODS
Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43 centigrade, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy, and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining.


RESULTS
All of the six treatment modalities down-regulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 +/- 0.009 vs 0.155 +/- 0.0115, P < 0.01) and Bcl-2 (0.086 +/- 0.010 vs 0.026 +/- 0.0170, P < 0.01) and up-regulating Bax expression (0.091 +/- 0.0013 vs 0.207 +/- 0.027, P < 0.01) compared with any single therapy.


CONCLUSIONS
Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.
Liang
Han
H
Department of Gastrointestinal Oncological Surgery, Tianjin Cancer Hospital, Tianjin Medical University, Tibyanbei Hexi District, Tianjin 300060, China. tjlianghan@126.com
Zhan
Hong-Jie
HJ
Wang
Bao-Gui
BG
Pan
Yuan
Y
Hao
Xi-Shan
XS
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D008297:Male; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011878:Radiotherapy / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein
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