4 OP Makarova
that arginine promotes tumor growth and enzymatic degradation of this amino
acid mediated arginase inhibits proliferation and death of tumor cells [12].
Arginase and NO-synthase pathways compete with each other for arginine.
Activation of NO-synthase pathway may contribute to the elimination of
tumor cancer cells. It has been established that the combined use of 5-
fluorouracil and L-arginine in nude mice bearing hepatocarcinoma leads to rise
of expression of inducible NO-synthase, NO (nitrogen oxide) levels in the
tumor, thus increasing gene expression of proteins that induce tumor cell
apoptosis [13]. Application of NO-synthase inhibitor L-NAME (methyl ester
of N-ω-nitro-L-arginine) reduces the effect of anticancer therapy [14]. Effect
of lithium carbonate nanosized particles injected after transplantation
hepatocarcinoma 29 cells in the thigh muscle, was aimed at increasing the NO
levels in tumors and peritoneal macrophages, which could lead to lower the
arginine levels required for tumor growth [15].
Treatment of hepatocarcinoma mice with nanosized particles of lithium
carbonate maintains of balance between oxidants and antioxidants and may
help limit the progression of precancerous condition toward malignancy and
tumor growth [16]. Tumor growth after hepatocarcinoma-29 cells injection
into muscle right leg changes the levels of lipid peroxidation activity in two-
phase manner. The level of 2-thiobarbituric acid-active products is decreased
in comparison with the control indicates after invasion of tumor cells, it is
raised at excessive tumor growth and diminish at terminal stage. Catalase
activity is elevated significantly, but superoxiddismutase activity is reduced in
tumor at hepatocarcinoma growth. The repeated injections of lithium
carbonate nanosized particles at hepatocarcinoma inhibit lipid peroxidation in
tumor tissue, but don’t influence on catalase and superoxiddismutase
activities.
Treatment with lithium carbonate officinal forms of two kinds of tumor-
bearing mice (hepatoma H22 and sarcoma S180) for 17 or 10 days (advanced
and simultaneous administration) significantly inhibit the growth of the two
kinds of tumor, and increase the activity of superoxide dismutase and decrease
the contents of malonyldialdehyde [17].
Many epithelial cancers, particularly gastrointestinal tract cancers, remain
poor prognosis diseases, due to resistance to cytotoxic therapy. An official
form of lithium carbonate was shown to induce autophagosomes in esophageal
and colorectal cancer cells by western blot analysis of LC3 isoforms,
morphology and FACS (fluorescence-activated cell sorting) quantitation of
Cyto-ID or mCherry-GFP-LC3 [18]. When combined with the
chemotherapeutic agent 5 - fluorouracil or oxaliplatin, lithium carbonate