The impact of hyperthermic chemotherapy on human gastric cancer cell lines: preliminary results.
In this preliminary study, we evaluated the impact of hyperthermia (HT) and hyperthermic chemotherapy (HTCT) on six human gastric cancer cell lines and explored the mechanisms of cell-killing effect under HTCT. Treatment conditions were categorized into 4 modes: i) normothermic control (NT), ii) HT, iii) normothermic chemotherapy (NTCT) and iv) HTCT. According to the data of MTT and LM observations, isolated HT only temporarily inhibited cell proliferation and had no cell-killing effect on gastric cancer cell lines employed in our study except for SNU-1. Combining with HT enhanced the cytotoxicity of CDDP in all gastric cell lines and the concentration inhibiting cell proliferation and inducing cell death of HTCT was much lower than that of NTCT. There was a synergistic effect of HT and chemotherapy on inhibiting proliferation in each cell line in a certain range of CDDP concentration. The data of TEM and FCM proved that HTCT induced cell death with two modes - apoptosis and necrosis, and apoptosis was the major type. Microarray illustrated that, under HTCT, a total of 58 gene expressions were regulated according to the filtering criteria, including 10 extra genes with an expression change below the threshold or even unchanged when treated with either HT or CDDP alone. Five of these 10 genes were verified by QRT-PCR. These genes may include the target genes for the enhancing effect of HT on chemotherapy and their effects should be further validated by functional analysis.
Tang
Rui
R
Department of General Surgery, Shanghai Institute of Digestive Surgery, RuiJin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Zhu
Zheng Gang
ZG
Qu
Ying
Y
Li
Jian Fang
JF
Ji
Yu Bao
YB
Cai
Qu
Q
Liu
Bing Ya
BY
Yan
Min
M
Yin
Hao Ran
HR
Lin
Yan Zhen
YZ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced; D009336:Necrosis; D013274:Stomach Neoplasms / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002945:Cisplatin