β—adrenergic agonist （1—isoproterenol）とphosphodiesterase inhibitor （papaverine）によるラットgliomaの治療

TREATMENT OF RAT GLIOMA WITH A β-ADRENERGIC AGONIST AND A PHOSPHODIESTERASE INHIBITOR IN Vivo

　抄録　ラットC6 glioma細胞はβ-adrenergic receptorを持つことが知られており，また同細胞はこれにより細胞内cyclic adenosine monophosphate （cAMP）濃度の量的変化を通して細胞の増殖を調節していると考えられている。そこで，β-adrenergic agonistである1-isoproterenolおよびphosphodiesteraseinhibitorであるpapaverineをin vivoにおいてC6 glioma細胞に作用させることにより，これらの薬剤の細胞増殖抑制効果を検討した。その結果，C6細胞を用いて作成した皮下モデルにおいて，これらの薬剤により腫瘍の増殖が有意に抑制されるのと同時に，脳腫瘍モデルとして作成したmeningeal gliomatosis（MG）ラットの生存日数も有意に延長した。これにより，このような細胞内cAMP濃度を増加させる薬剤により脳腫瘍細胞の増殖を抑制し，ひいては脳腫瘍モデルラットの生存日数を延長することが可能であることが示唆された。

Rat C 6 glioma is known to possess a ,β-adre-nergic recepror with which intracellular cyclic adenosine monophosphate (cAMP) levels are alter-ed to control cell growth in vitro. In order to study the effect of β-adrenergic agonist, isoprote-renol, in growth-inhibitory action upon C 6 glioma cells, subcutaneous tumor models and meningeal gliomatisis (MG) models as a brain tumor model have been exposed to the treatment of isoprote-renol. Growth of subcutaneous tumor was suppres-sed by the treatment of the drug, and the survival time of MG rats was prolonged by the intrathe-cal (i. t.) injection of isoproterenol. The addition of papaverine, phosphodiesterase inhibitor, to the treatment schedule augmented the growth-inhibi-tory effect of isoproterenol. Therefore, it is con-cluded that the survival time of the brain tumor models could be prolonged through the inhibition of the growth of C 6 glioma cells by such drugs as those which elevate intracellular cAMP levels.

Appreciation is extended to Dr. Takao Hoshino for gift of C 6 glioma cells. We are indebted to Mrs. Rosalind Yoshida for editing the manuscript.

This work was supported in part by a Grant-Aid Cancer Research from the Japanese Ministry of Health and Wel-fare (No. 58480304).