| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
In order to develop an assay for predicting sensitivity to anticancer drugs, we evaluated the telomerase activity and expression of human telomerase reverse transcriprase (hTERT) gene using human gastric and breast cancer cell lines.
Doxorubicin (DOX), 5-fluorouracil (5-FU), cis-platinum (CDDP) and irinotecane (CPT-11; SN-38) were added to the culture of human gastric and breast cancer cell lines (3 types each), and then cell number, cell cycle, telomerase activity and expression of hTERT mRNA were serially measured. In DOX, 5-FU and CDDP treated group, telomerase activity and expression of hTERT mRNA gradually decreased in accordance with antitumor effect. However, transient increase in telomerase activity and hTERT expression were observed 24 hr after drug treatment in CPT-11 treated group. There was no correlation between the changes in cell cycle and telomerase activity nor hTERT mRNA expression. There also was no relationship between antitumor activity and expression of human telomerase RNA subunit nor human telomerase protein p80.
Human gastric cancer cell line MKN-28 was transplanted to nude mouse and in vivo experiment was also carried out. Similar to the results obtained from in vitro experiment, gradual decrease in telomerase activity and hTERT mRNA expression were obtained after treatment by DOX, 5-FU and CDDP. On the contrary, transient increase in telomerase activity and hTERT mRNA expression were also observed by CPT-11 treatment.
From these results, hTERT is supposed to be the most important factor which regulate the telomerase activity. In most of anticancer drugs, telomerase activity and hTERT mRNA expression decreased in accordance with antitumor effect. However, transient increase was also observed in certain kind of anticancer drug. Therefore, we have to be careful to apply this assay system for clinical test.
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