In order to study the antineoplastic effect of Prostaglandin (PG) derivatives on the tumors in the central nervous system, basic experiments were carried out in in vitro and in vivo system. PGs used were PGD
2, PGJ
2, and 4
12PGJ
2. The subjects were an established brain tumor cell line, U373MG, and T
9 rat glioma cell line.
The aim of the present study was to stud y whether these derivatives possessed antitumoral effect on brain tumors and, if so, to clarify the mechanism of their antineoplasticity. Established T
9 cell line derived from rat glioma and U373MG derived f rom human glioma were used as the target cells.
All derivatives, PGD
2, PGJ
2, and Δ
12PGJ
2, showed significant growth inhibitions on cultured cells dose-dependently, and Δ
12PGJ
2 was most effective, followed by PGJ
2 and then PGD
2.
In chronological observation of the growth inhibition and changes in the viabilitiy, early growth inhibition and decrease of the viability were observed in the order of Δ
12PGJ
2, PGJ
2 and then PGD
2. At low concentration, however, regrowth of the cells was observed somehow as time passed.
Changes of the DNA-histogram were studied using flow cytometer (FCM). Cells at the G
2 -FM phase and S phase decreased in number, while rate of the cells at G
0/G
1 phase increased. At low concentration the cell returned to the proliferative pattern as before as time passed, while at high concentration such tendency was not observed, suggesting stop of the cell cycle.
Antineo plastic effect appeared at rather earlier phase,6 to 9 hours after contact with Δ
12PGJ
2, and the author could confirm that G
1 phase blocking started prior to decrease of the viability.
According to the study of the effect of PG derivatives on the cell kinetics of the established brain tumor cell lines by the double staining method with bromodeoxyuridine (BrdU)and DNA, it was clearly shown that cells at the S and G
2 M phase decreased, while rate of those at G
0/G
1 phase increased in all three prostaglandins, PGD
2, PGJ
2, and Δ
12 PGJ
2h. e decrease of the cells at the S phase in which BrdU was taken was clarified by the present study.
Morphologically, different from the changes due to other antineoplastic agents such as ACNU, changes of the cytoplasm such as vacuolization of the cytoplasm or disappearance of the cell processes were prominent but changes of the nuclei were rare.
Growth inhibition on subcutaneously transplanted brain tumor cell s was studied in rats. In the group receiving intratumoral injection of Δ
12PGJ
2 (4mg/kg), antineoplastic effect was observed, while no effect was observed in the intraperitoneally injected group.
From above results, the author concluded that Prostaglandin had significant antineoplastic effect on cultured brain tumor cells, and the essential substance for the action of the antineoplastic effect was Δ
12PGJ
2. Clinical application of Δ
12PGJ
2 among other PG derivatives was expected for the treatment of malignant brain tumor patients.
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