1995 Fiscal Year Final Research Report Summary
BASIC STUDIES ON ANTITUMOR EFFECT OF N-MYC ANTISENSE OLIGOMERS ON CANCER CELL LINES WITH N-MYC AMPLIFICATION
| Project/Area Number |
06670604
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
MIZUSHIMA Yutaka TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY FIRST DEPARTMENT OF INTERNAL MEDICINE,LECTURER, 医学部, 講師 (20174021)
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| Project Period (FY) |
1994 – 1995
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| Keywords | N-MYC / ONCOGENE / ANTISENSE OLIGOMERS / LUNG CANCER / DRUG RESISTANCE |
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| Research Abstract |
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).
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