Study On Antitumor Activity And Mechanisms Of Allotri-tridecyl Diethylamine

Objective: To investigate antitumor effect of Allotri-tridecyl diethylamine (D-108) in vivo & vitro, and to explore the mechanisms of antitumor effects.Methods: The cytotoxic effects of D-108 on various tumor cell lines cultured in vitro were determined with trypan blue dye exclusion test, MTT method and growth curve method. At a tolerable dose level, D-108 was administrated to treat mice transplanted solid tumors U14 and ascetic tumors HAC, tumor weight and survival time were observed. The acute toxicity of mice were observed by different administration route of D-108. Apoptosis morphological transformation of HL 60 cell induced by D-108 was detected by the phase contrast microscope, Giemsa staining and AO-EB staining. Alteration of cell cycle was analyzed by flow cytometer. DNA ladder was detected with agarose gel electrophoresis. The enzymatic activity of Caspase-3, Caspase-8 and Caspase-9 were assayed by colorimetric.Results: D-108 induced significant growth arrest in various malignant tumor cell lines cultured in vitro . IC50 of these cells exposed to the drug for 48 hours ranged from 0.22 to 2.19μg/mL. D-108 intraperitoneal injection(i.p., 12 mg·kg^-1·d^-1) and intragastric administration(i.g., 100 mg·kg^-1·d^-1) could effectively inhibit in vivo growth of mice implanted solid tumor U14 ,and subcutaneous injection(i.p., 20 mg·kg^-1·d^-1) and i.g.(100 mg·kg^-1·d^-1) could increase survival time implanted ascetic tumors HAC of mice. LD50 of D-108 was 43.7mg/kg(i.p.), 230.9mg/kg (s.c.),...