Establishment and gene analysis of an oxaliplatin-resistant colon cancer cell line THC8307/L-OHP.
Oxaliplatin is widely used for chemotherapy of several malignancies, especially of colon cancer. As the mechanism of resistance to oxaliplatin is unclear, we established an oxaliplatin-resistant cell line, THC8307/L-OHP, from an oxaliplatin-sensitive colonic cancer cell line, THC8307. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay indicated that THC8307/L-OHP has 30.99-fold greater resistance to oxaliplatin than THC8307. Analyzing its gene expression profile using an in-house oligomicroarray, a number of genes were differentially expressed in the THC8307/L-OHP cells, compared with parental cells (THC8307). Proapoptotic genes such as STK17A and BNIP3 were significantly downregulated, whereas the genes PSAP and GDIA1, which were involved in antiapoptosis, were overexpressed. Moreover, the THC8307/L-OHP cells are also resistant to the other anticancer drug 5-fluorouracil, and the expression levels of the differentially regulated genes such as S100P, CAeta, STA15, TCF8 are constantly maintained. These results provide clues for understanding the oxaliplatin-resistant mechanisms and imply markers to predict drug sensitivities for 'personalized chemotherapy'.
Tang
Hua
H
Tianjin Life Science Research Center, Tianjin Medical University, Tianjin, PRC. htang2002@yahoo.com
Liu
Yuan-Jun
YJ
Liu
Min
M
Li
Xin
X
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin