Pentoxifylline promotes development of murine colon adenocarcinoma-derived metastatic tumors in liver.
Pentoxifylline is commonly used in the treatment of peripheral vascular diseases. It improves microcirculatory flow and tissue perfusion. Moreover, pentoxifylline displays some immunomodulatory properties that presumably might affect the anticancer response. Therefore, the aim of the present study was to evaluate the influence of pentoxifylline on tumor development. Balb/c mice were injected with murine colon adenocarcinoma C-26 cells intravenously, into the vena portae, and divided into two groups. Mice from the experimental groups received daily intraperitoneal injections of pentoxifylline (30 mg/kg) while the controls were injected with 0.9% NaCl. Two weeks after C-26 cell inoculation mice were sacrificed and autopsy was performed. It was found that the livers of control animals revealed only several small tumor foci, whereas the livers of pentoxifylline-treated mice displayed numerous cancerous outgrowths. The mean liver weight in pentoxifylline group was 2.21+/-0.62 g as compared to 1.36+/-0.15 g in controls (P=0.004). Moreover, the influence of pentoxifylline on murine and human cell line proliferation in vitro was evaluated. It has been observed that pentoxifylline, at pharmacologically achievable concentrations, stimulated the proliferation of murine (C-26) and human (CaSki, U-937) cell lines. However, it did not stimulate human melanoma (WM-35) cell proliferation. Since there has been no evidence so far that pentoxifylline may promote tumor progression, it is still considered to be a safe drug. Moreover, some beneficial properties of pentoxifylline, which could be useful in cancer treatment, have been reported and a few clinical trials with oncological patients have been performed. Surprisingly, our study revealed that pentoxifylline significantly promoted C-26-derived metastatic tumor growth in liver. Although this model might be unique in its sensitivity to tumor-promoting effects of pentoxifylline, it cannot be excluded that similar effects might occur in some cases of tumors developing in humans. Such effects could be relevant, since the stimulatory influence of pentoxifylline on proliferation does not appear to be species- or tissue-specific.
Grzela
Tomasz
T
Department of Histology and Embryology, Center of Biostructure Research, The Medical University of Warsaw, PL 02 004 Warsaw, Poland. tgrzela@ib.amwaw.edu.pl
Lazarczyk
Maciej
M
Niderla
Justyna
J
Golab
Jakub
J
Lazarczyk
Marta Alicja
MA
Skopinski
Piotr
P
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010431:Pentoxifylline / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D020298:U937 Cells
D004396:Coloring Agents; D016166:Free Radical Scavengers; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D010431:Pentoxifylline