ADENOVIRAL TRANSFER OF FHIT GENE TO LUNG CANCER

为了评价体内转导人FHIT基因对肺癌细胞的抑制作用，我们构建了携带人FHIT基因的重组腺病毒载体(AdCMVFHIT)。体外转染人FHIT基因后，在mRNALEVEL上检测了FHIT基因的表达。NORTHERN分析揭示了FHIT基因在A549细胞中的转录产物。此外，高效液相分析表明，功能性FHIT蛋白与AR3A反应。WE评估了AdCMVFHIT感染VITRON后A549细胞的生长(P&lt；结论在裸鼠A549裸鼠皮下直接注射AdCMVFHIT后，肿瘤体积在第20天缩小了47%，在第24天缩小了51%(P=0.023和P=0.013)，提示局部转导人FHIT基因有可能成为控制肺癌生长的一种策略。

TO EVALUATE THE CONCEPT THAT IN VIVO TRANSFER OF THE HUMAN FHIT GENE WILL SUPPRESS THE LUNG CANCER CELLS, WE CONSTRUCTED AN ADENOVIRUS VECTOR (AdCMVFHIT) CARRYING THE HUMAN FHIT GENE DRIVEN BY THE CMV PROMOTOR.THE EXPRESSION OF THE FHIT cDNA FOLLOWING IN VITRO TRANSFER WITH THE AdCMVFHIT VECTOR WAS EVALUATED AT THE mRNALEVEL.NORTHERN ANALYSIS REVEALED mRNA TRANSCRIPTS OF THE FHIT cDNA IN A549 CELLS.IN ADDITION, HPLC ANALYSIS SHOWED FUNCTIONAL FHIT PROTEIN RESPONDED WITH AR3A.WE EVALUATED THE GROWTH OF A549 CELLS FOLLOWING INFECTION WITH AdCMVFHIT IN VITRO.THE INFECTED CELLS WERE SIGNIFICANTLY SUPPRESSED IN COMPARISON WITH CONTROL (P<0.05).CONSISTENT WITH THESE IN VITRO OBSERVATIONS, WHEN AdCMVFHIT WAS DIRECTLY INJECTED INTO ESTABLISHED SUBCUTANEOUS A549 TUMORS IN NUDE MICE, THERE WAS 47% REDUCTION WITH IN TUMOR SIZE AT DAY 20 AND A 51% AT DAY 24 (P=0.023 AND P=0.013).THESE OBSERVATIONS SUGGEST THAT LOCAL GENE TRANSFER OF THE HUMAN FHIT GENE MAY HAVE POTENTIAL AS A STRATEGY FOR CONTROL OF GROWTH OF LUNG CANCER.