title: Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo.
abstract: Modulation of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the clinical outcome of cancer treatment. Bax, an apoptosis-promoting member of the bcl-2 family, may be a key factor influencing the chemosensitivity of tumor cells, however, its involvement in cellular sensitivity to anti-cancer drugs remains uncertain in squamous cell carcinoma (SCC). To investigate the role of bax gene expression in modulating cisplatin (CDDP)-induced apoptosis in vitro, an established CDDP-resistant human head and neck SCC (IMC-3 cell line) was transfected with bax gene-bearing mammalian expression vector. Overexpression of the bax gene in CDDP-resistant IMC-3 cells elevated the CDDP susceptibility of tumor cells to a level similar to that of the parental IMC-3 cells. In an in vivo study, percutaneous transfer of apoptosis-promoting bax gene by particle-mediated (gene gun) delivery caused overexpression of Bax in SCC, which was confirmed by immunohistochemical staining, and inhibited the growth of mouse CDDP-resistant SCC. Furthermore, combination therapy with bax gene transfer and subcutaneous administration of CDDP at 3-day intervals markedly inhibited the growth of mouse SCC. Thus, overexpression of bax in SCC by a gene gun system appears to be a rational approach to improving the efficacy of chemotherapy and treatment outcome. We suggest that exogenous bax expression may have therapeutic applications for enhancing chemotherapy in SCC.
authors.affiliation: Department of Otorhinolaryngology, Fukui Medical University, Fukui, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Sugimoto
authors.forename: S
authors.initials: S
authors.lastname: Fujieda
authors.forename: M
authors.initials: M
authors.lastname: Seki
authors.forename: H
authors.initials: H
authors.lastname: Sunaga
authors.forename: G K
authors.initials: GK
authors.lastname: Fan
authors.forename: H
authors.initials: H
authors.lastname: Tsuzuki
authors.forename: C
authors.initials: C
authors.lastname: Borner
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Matsukawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D008441:Maxillary Neoplasms; D051379:Mice; D008809:Mice, Inbred C3H; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D002945:Cisplatin