Study of the effect of 1-({4-[(2,4-dichlorobenzoyl)amino]phenyl}sulfonyl-(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid (GGM-27) on tumor growth and survival in BALB/c mice bearing ACATOL colon adenocarcinoma in comparison with doxorubicin

Introduction. Matrix metalloproteinases (MMPs) belong to the family of zinc-dependent endopeptidases capable of degrading the main components of extracellular matrix proteins that form the basis of connective tissue; they are also involved in many pathological processes in the body. MMP-2 is actively expressed in lung cancer tissues, while MMP-2 and MMP-9 play a significant role in the development of colorectal cancer.

Objective. To evaluate the effect of 1-({4-[(2,4-dichlorobenzoyl)amino]phenyl}sulfonyl-(2S,4R)-4-hydroxypyrrolidine-2 carboxylic acid (GGM-27) on tumor growth and survival in BALB/c mice using the AKATOL colon adenocarcinoma model.

Materials and methods. AKATOL colon adenocarcinoma was implanted subcutaneously into the axillary region of male BALB/c mice at a dose of 1×10⁶ cells. From day 2 to day 15 of tumor development, GGM-27 was administered intraperitoneally (i.p.) at doses of 1 mg/kg and 10 mg/kg. Doxorubicin was used as a reference drug, administered at a dose of 5 mg/kg i.p. on days 2 and 4 of tumor development. The antitumor activity of GGM-27 was assessed by tumor growth inhibition (TGI) and lifespan extension (LSE).

Results. After a 14-day course of i.p. administration of GGM-27 at a dose of 1 mg/kg, TGI was 72.8 % on day 21 of the experiment and 71 % on day 28. After i.p. administration of GGM-27 at a dose of 10 mg/kg, TGI was 63 % on day 21 and 56% on day 28. LSE after a course of GGM-27 at a dose of 10 mg/kg was 24 %. After two i.p. administrations of doxorubicin at a dose of 5 mg/kg, TGI was 82 % on day 21 and 69 % on day 28; however, two of the 12 animals died due to drug toxicity.

Conclusions. Administration of 1-({4-[(2,4-dichlorobenzoyl)amino]phenyl}sulfonyl-(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid at a dose of 1 mg/kg caused TGI. On day 21 of the experiment, with GGM-27 administration, TGI was 73 %, and on day 28, TGI was 71 %.

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