UETA Eisaku Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部・附属病院, 助手 (10203431)
YAMAMOTO Tetsuya Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部・附属病院, 講師 (00200824)
YONEDA Kazunori Kochi Medical School, Department of Oral Surgery, Associate Professor, 医学部, 助教授 (90182849)
KIMURA Tsuyoshi Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部・附属病院, 助手 (10294836)
|Budget Amount *help
¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1999 : ¥1,100,000 (Direct Cost : ¥1,100,000)
To develop multidisciplinary therapy of cancers, we tried in vitro to induce differentiation and apoptosis of established squamous cell carcinoma (SCC) cells. The SCC cells were treated with differentiation-inducing agents (TGF- β and vesnarinone), anti-cancer drugs (5-FU and peplomycin), γ -rays and IL-2-activated killer lymphocytes (LAK cells) and the mechanism of differentiation and apoptosis was analyzed by investigating the cell phase, the expression of cell cycle-regulating proteins such as p53, cyclin-dependent kinase-inhibitor p9- 1, cyclin D and E, and Bcl-2 family proteins, intracellular and intramitochondrial reactive oxygen intermediates (ROI) and activation of caspases. As the result, followings were obtained.
1, TGF-β and vesnarinone induced a G1 arrest, which resulted in differentiation of SCC cells in a p53-independent manner.
2, Apoptosis but not differentiation was induced by 5-FU, peplomycin and γ-rays. Additive and multiplicatire effects were observed by a combination treatment of cells with the anticancer drugs and γ-rays, and LAK cells and γ-rays, respectively.
3, Apoptosis-induced by LAK cells depended on the caspase-3 activation by granzyme B and the signal from Fas and also depended on the cytochrome c release from mitochondria which was induced by intramitochondrial ROI.
These results suggest that multidisciplinary therapy composed of immuno-chemo-radio-agents is rather effective to SCC although the details in the cooperation of these agents remain to be clarified. In fact, oral SCCs which were treated with chemo-radiotherapy with adoptive LAK therapy revealed better prognosis than SCCs treated without LAK therapy.