Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 21, 2012; 18(7): 646-653
Published online Feb 21, 2012. doi: 10.3748/wjg.v18.i7.646
Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma cells
Xiang-Liang Zhang, An-Bin Hu, Shu-Zhong Cui, Hong-Bo Wei
Xiang-Liang Zhang, Hong-Bo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
An-Bin Hu, Department of General Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Shu-Zhong Cui, Department of Abdominal Surgery, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China
Author contributions: Zhang XL and Hu AB contributed equally to this work; Cui SZ and Wei HB supervised the experiment; Zhang XL and Hu AB wrote and revised the paper; All authors read and approved the final manuscript.
Supported by The Guangdong Provincial Science and Technology Programs, China, No. 2009A030301013; the Scientific Funds of Guangzhou Medical College, China, No. 2010A29; National Natural Science Foundation of China, No. 30700398 and 81172831; Natural Science Foundation of Guangdong Province, No. 10151008901000200
Correspondence to: Hong-Bo Wei, Professor, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China. drwhb@21cn.com
Telephone: +86-20-85252287 Fax: +86-20-85252258
Received: June 11, 2011
Revised: September 28, 2011
Accepted: October 5, 2011
Published online: February 21, 2012
Abstract

AIM: To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells.

METHODS: The human colon adenocarcinoma cell line Lovo was obtained from Sun Yat-Sen University. Cells were sealed with parafilm and placed in a circulating water bath, and was maintained within 0.01  °C of the desired temperature (37  °C, 39  °C, 41  °C, 43  °C and 45  °C). Thermal therapy was given alone to the negative control group while oxaliplatin was administered to the treatment group at doses of 12.5 μg/mL and 50 μg/mL. Identification of morphological changes, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and Western blotting were used to investigate the effect of thermochemotherapy on human colon adenocarcinoma Lovo cells, including changes in the signal pathway related to apoptosis.

RESULTS: A temperature-dependent inhibition of cell growth was observed after oxaliplatin exposure, while a synergistic interaction was detected preferentially with sequential combination. Thermochemotherapy changed the morphology of Lovo cells, increased the inhibition rate of the Lovo cells (P < 0.05) and enhanced cellular population in the G0/G1 phase (16.7% ± 4.8 % in phase S plus 3.7% ± 2.4 % in phase G2/M, P < 0.05). Thermochemotherapy increased apoptosis through upregulating p53, Bax and downregulating Bcl-2. Protein levels were elevated in p53, Bax/Bcl-2 in thermochemotherapy group as compared with the control group (P < 0.05).

CONCLUSION: Thermochemotherapy may play an important role in apoptosis via the activation of p53, Bax and the repression of Bcl-2 in Lovo cells.

Keywords: Colorectal cancer; Oxaliplatin; Thermochemotherapy; Mitochondrial apoptotic pathway