ADENOVIRAL TRANSFER OF FHIT GENE TO LUNG CANCER

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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.