Apoptosis induced by 5-fluorouracil, cisplatin and paclitaxel are associated with p53 gene status in gastric cancer cell lines.
In a recent study, we evaluated the efficacy and toxicity of 5-fluorouracil (5-FU), cisplatin (CDDP), and 5-FU plus CDDP (FP treatment) in gastric cancer cell lines and examined the relationship between the response to FP treatment and apoptosis. Our study indicated that there may be prognostic value in measuring p53 prior to FP treatment, and that cancers with wild-type p53 may be better candidates for FP treatment than those with mutant-type p53 in gastric cancer patients. In the present study, because cells with mutant-type p53 are suggested to be less responsive to FP chemotherapy treatment, we examined the relationship between the response to paclitaxel and apoptosis in MKN45 and MKN28 human gastric cancer cell lines by flow cytometry. In both MKN45 and MKN28 cells, paclitaxel arrested cells in the G2/M phases of the cell cycle after 24 h. Additionally, in both MKN45 and MKN28 cells, paclitaxel produced a significant rise in the number of subG1-phase cells after 72 h by the flow cytometry histogram. From these results, our previous study suggests that cells with mutant-type p53 may be less responsive to FP treatment and the present study indicates that another anti-cancer drug like paclitaxel, which might be mediated by a p53-independent pathway, should be selected. These insights may provide a new strategy for gastric cancer chemotherapy, especially second-line chemotherapy or adjuvant chemotherapy.
Matsuhashi
Nobuhisa
N
Department of Surgical Oncology, Gifu University School of Medicine, Gifu City 501-1194, Japan. nobuhisa517@hotmail.com
Saio
Masanao
M
Matsuo
Atsushi
A
Sugiyama
Yasuyuki
Y
Saji
Shigetoyo
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D016158:Genes, p53; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil