|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1994 : ¥1,000,000 (Direct Cost : ¥1,000,000)
1)The association between gene alterations(K-ras, p53, *N-myc)and drug resistance (CDDP, CBDCA, MMC Epi-ADM) was examined in 29 human lung carcinoma cell lines using the m vitro MTT assay. There was no significant difference in the IC50 values of four drugs between K-ras or p53 gene alteration-positive and-negative groups. However, two cell lines with N-myc amplification (H-69, SBC-4) showed a higher resistance than those without N-myc amplification to all four drugs. This preliminary study suggests that N-myc gene alteration might be related to drug resistance (Oncology Rep., 2 : 277-280, 1995).
2)To make more clearly the association between N-myc gene and drug resistance, we examined the effect of continuous in vitro exposure to CDDP on the degree of N-myc amplification using H-69 and SBC-4 cell lines. Result was that the amplification of the N-myc gene did not change by CDDP exposure. Therefore, we concluded that the degree of CDDP resistance might not correlate with the degree of amplification or over expression of the N-myc gene, if activation of the N-myc would be related (Oncology, 53 : 417421, 1996).
3)Effect of N-myc antisense oligodeoxynucleotide (ODN) on the proliferation of tumor cells and its combined antitumor effect with CDDP were examined in vitro on human lung cancer cell lines with N-myc amplification. A significant difference in the anti-proliferative effect between antisense QDN and sense ODN treatment was observed only on tumor cells with N-myc amplification. However, pretreatment and posttreatment with antisense ODN showed no beneficial effects on CDDP cytotoxicity. Pretreatment with antisense ODN showed a tendency to reduce rather than enhance CDDP cytotoxicity. This study suggests that antisense ODN may not be beneficial when combined with chemotherapy (Anticancer Res., 15 : 37-44, 1995).