Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin In vitro and In vivo

✍ Scribed by Chizuru Sugimoto; Shigeharu Fujieda; Mizue Seki; Hiroshi Sunaga; Guo-Kang Fan; Hideaki Tsuzuki; Christoph Borner; Hitoshi Saito; Shigeru Matsukawa

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 638 KB
• Volume: 82
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990909)82:6<860::aid-ijc15>3.0.co;2-6

✦ Synopsis

Modulation of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the clinical outcome of cancer treatment. Bax, an apoptosispromoting 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 CDDPresistant 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 apoptosispromoting 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.