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World J Gastroenterol. Aug 28, 2007; 13(32): 4365-4371
Published online Aug 28, 2007. doi: 10.3748/wjg.v13.i32.4365
Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice
Han Liang, Hong-Jie Zhan, Bao-Gui Wang, Yuan Pan, Xi-Shan Hao
Han Liang, Hong-Jie Zhan, Bao-Gui Wang, Xi-Shan Hao, Yan Pan, Department of Gastrointestinal Oncological Surgery, Tianjin Cancer Hospital, Tianjin Medical University, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Author contributions: All authors contributed equally to the work.
Supported by the Clinical Research Foundation of Tianjin Medical University, No. 2002KY18
Correspondence to: Han Liang, Professor, Department of Gastrointestinal Oncological Surgery, Tianjin Cancer Hospital, Tianjin Medical University, Tibyanbei Hexi District, Tianjin 300060, China. tjlianghan@126.com
Telephone: +86-22-23340123 Fax: +86-22-23359984
Received: April 19, 2007
Revised: May 17, 2007
Accepted: May 22, 2007
Published online: August 28, 2007
Abstract

AIM: 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°C, 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.

CONCLUSION: Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.

Keywords: Hyperthermia; Apoptosis; p53; Bcl-2; Bax; Nude mice; Colon cancer; Cell line