비소세포폐암 세포주에 대한 아데노바이러스 매개 p53 유전자 전이요법의 제한적 효과
Limited Cytotoxic Effect of Adenoviral-mediated p53 Gene Transfer in Variable Non-small Cell Lung Cancer(NSCLC) Cell Lines
대한암학회지 1997년 29권 4호 p.565 ~ 575
소속 상세정보
김진국/Jhin Gook Kim
이숙현/황은성/김종식/김관민/이제호/김진국/김관민/Sook Hyun Lee/Eun Sung Hwang/Jong Sik Kim/Kwhan Mien Kim/Je Ho Lee/Jhin Gook Kim/Kwhan Mien Kim
KMID : 0360319970290040565
Abstract
결론
아데노 바이러스를 이용한 p53유전자 치료가 여러 폐암세포주에 대해 두루 기대되는 항
암효과를 나타내는 지 실험한 결과, p53유전자가 결핍된 세포주들에서 두드러진 효과를 보
인 용량의 Avp53의 감염에도 불구하고 폐암세포주들 중 p53유전자가 정상인 경우에는
Avp53 감염에 의한 cytotoxicity가 거의 나타나지 않았으며, p53유전자가 변이된 경우에도
50% 이상의 세포주들에서 미약한 정도의 효과만을 관찰할 수 있었으며, 유전자 주입 후
p21 단백이 발현한 경우 뚜렷한 효과를 볼 수 있었다. 이상의 실험 연구를 토대로, 비소세포
폐암에 있어, 아데노바이러스 매개 p53유전자 전이요법의 단독 치료로는 적용대상 범위나
그 효과에 제한이 많으리라고 예상되며, 따라서 환자군 중 50%에 달하는 정상 p53유전자를
가진 환자에 있어 적용가능한 방법의 개발이 시급하다고 사료된다.
#초록#
Purpose: Cancer gene therapeutic strategy using p53 rumor suppresser gene have been
suggested to be effective in many solid tumors including non-small cell lung
cancer(NSCLC). To test generalized applicability, we tested a number of non-small cell
lung cancer cell lines for their sensitivity to adenoviral-mediated wild-type p53 gene
transfer.
Materials and Method: Replication-incompetent recombinant adenovirus encoding
wild-type p53(Avp53) under the control of the human cytomegalovirus(CMV) promoter
was constructed and the cytotoxic effectiveness was evaluated in various NSCLC cell
lines. Because 20 moi(multiplicity of infection; number of active virus particle/cell
number) of Avp53 showed highly-effective cytotoxicity in p53-deleted cell
lines(NCI-H1299, and NCI-H358), same amount was used for other cell lines.
Results: Variable degree of cytotoxicity were observed in cell line with p53 mutation,
but almost no effect were observed in those with will-type p53. Neither the infectivity
of adenovirus, which was observed by x-gal stain after adenoviral mediated lac Z gene,
nor the expression of p53 protein in infected cell, which was observed by western blot,
was not the useful marker to expect the cytotoxic effect of Avp53. However, in
responsive cell lines with Avp53, prominent expression of p21 protein, which was
observed by western blot, was noticed.
Conclusion: In conclusion, adenoviral-mediated wild-type p53 transfer may not be
applicable to every patient with non-small cell lung cancer, especially when the tumor
has wild-type p53 gene. Better method to predict the effectiveness before application and
strategy to widen the applicable extent is needed.
키워드
Non-small cell lung cancer cell lines; Adenoviral-mediated p53 gene transfer;
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