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Title   p53 유전자 변형이 발생한 위암세포주에서 유전자이상 교정에 의한 항암제 감수성 변화 ( Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53 )
Publicationinfo   1998 Jan; 030(03): 497-508.
Key_word   Wild-type p53, Chemo-sensitization, Etoposide, Cisplatin, Gastric cancer
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Abstract   Purpose: It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53. Materials and Methods: YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3Cⓒy(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis. Results: Even though p53 production hom the YCC-3Cⓒy cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3Cⓒy cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3Cⓒy cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3Cⓒy cell lines after cisplatin treatment. Conclusion: Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.
저 자   맹호영(Ho Young Maeng),라선영(Sun Young Rha),민병소(Byung Soh Min),김용배(Yong Bae Kim),곽현주(Hyun Joo Kwak),김태수(Tae Soo Kim),박규현(Kyu Hyun Park),유내춘(Nae Choon Yoo),임호영(Ho Young Lim),최진혁(Jin Hyuk Choi),김주항(Joo Hang Kim),노재경(Jae Kyung Roh),민진식(Jin Sik Min),김병수(Byung Soo