H7, AN INHIBITOR OF PROTEIN-KINASE-C, INHIBITS TUMOR-CELL DIVISION INMICE BEARING ASCITIC EHRLICHS CARCINOMA

We have previously shown that H7, an inhibitor of protein kinase C (PK C), inhibits proliferation of several cell lines as well as of primary cultured cells from human tumours. The aim of this work was to assess whether H7 is able to prevent the division of tumour cells in mice be aring Ehrlich's ascitic carcinoma. The LD(50) of H7 injected intraveno usly was 61 mg/kg and 94 mg/kg for starved and fed mice, respectively. Acute intraperitoneal injection of 100 mg/kg of H7 decreased the numb er of mitoses in tumoral cells from ascitic fluid of mice bearing the carcinoma. The reduction was maximal (approximately 50%) after 90 min and then the number of mitosis rose due to a decrease in H7. Continuou s delivery of H7 from miniosmotic pumps implanted on the backs of the mice reduced the number of mitoses by approximately 65%, and the effec t was maintained for approximately 24 h. The effect cannot be maintain ed for longer because H7 is unstable at body temperature. These result s indicate that inhibition of PKC can block division of tumour cells i n carcinoma-bearing animals, and support the idea that inhibitors of P KC could be useful for the clinical control of proliferation of certai n tumours.