Comparison of some antineoplastic drugs on inhibiting thrombin catalizing fibrinogen clotting in vitro.
OBJECTIVE
To classify the effect of thrombin, the key enzyme which enables fibrinogen to form fibrin (fibrinogen clotting) on the formation of metastasis by comparing the inhibition of some antineoplastic drugs on fibrinogen clotting in vitro.


METHODS
Time intervals of different drugs to reach a maximum OD (340 nm) data in fibrinogen solution added with thrombin were used in this work.


RESULTS
It was found that L-4-oxalysine (8-40 micrograms/ml) and arabinosyl cytosine (10-50 micrograms/ml) could inhibit the effect of thrombin by extending the fibrinogen clotting time to 100%-150% (P < 0.001) and 61%-100% (P < 0.001) while the other antimetastatic drugs razoxane, probimane, adriamycin, harringtonine homoharringtonine and alpha-anordrin at the treatment concentrations showed no such activity. The positive rate of drugs to thrombin activity was approximately 25%.


CONCLUSIONS
It suggests that L-4-oxalysine and arabinosyl cytosine may even exhibit antimetastatic effect through thrombin-fibrinogen pathway, and thrombin might operate in tumor metastasis for only limited step but crucial to fibrin formation in tumor nodules.
Lu
D
D
School of Life Sciences, Shanghai University, Shanghai 201800, China.
Cao
J
J
Huang
Y
Y
Gong
L
L
Chen
X
X
Chen
E
E
Xu
B
B
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002417:Cattle; D003561:Cytarabine / Q000494:pharmacology; D005340:Fibrinogen / Q000187:drug effects*; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000600:Amino Acids, Dicarboxylic; D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D005340:Fibrinogen; C027136:4-oxalysine; D013917:Thrombin