60 Background: Resistance to anti-cancer drugs is a critical issue in treatment of cancer. Alteration of gene expression profile accompanied with acquisition of drug-resistance is considered to be related with resistance mechanisms. Methods: 1. Ascitic fluids were collected before the beginning of CapeOX, during the treatment was effective, and after the disease was progressed. They were cultured for ten days and passed to new flasks, and were cultured in additional two weeks to remove normal cells including white blood cells and mesothelial cells. 2. AGS cells were cultured in medium with either fluorouracil or oxaliplatin, and fluorouracil- or oxaliplatin-resistant cells were established. AGS cells were also treated with a demethylating agent decitabine. 3. Expression of 25,147 genes was analyzed with microarray, and was compared among ascitic fluid cells before and after CapeOX, drug-resistant AGS cells, and decitabine-treated AGS cells. Results: Genes with alteration in expression due to CapeOX-resistance were classified into genes commonly changed with fluorouracil-resistant cells, those with oxaliplatin-resistant cells, and others. Among 873 genes with decreased expression after CapeOX, some genes including PCDH20 and DEFB4A have been reported as potential tumor suppressor genes. Expression of PCHD20 in AGS increased after treatment with decitabine. Conclusions: Drug-resistance in gastric cancer may be related with expression of genes including tumor suppressors regulated by epigenetic mechanisms. Repetitive collection of gastric cancer cells in ascitic fluids before and after chemotherapy is useful to understand drug-resistance mechanisms.
Acquired resistance mechanisms to afatinib in
HER
2
‐amplified gastric cancer cells