Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis.
Hepatocellular carcinoma is the most prevalent type of tumor among primary tumors affecting the liver. Rapamycin is currently used as a basis for chemotherapy in the treatment of cancers, including the liver. Because it shows several adverse effects, minimizing these effects without compromising efficacy is important. In this sense other drugs may be used concomitantly. One of these drugs is fructose-1,6-bisphosphate (FBP), which has shown therapeutic effect in various pathological situations, having antioxidant and anti-inflammatory proprieties. The objective of the present study was to evaluate the activity of rapamycin in combination with the FBP in HepG2 cell proliferation and the mechanisms involved. HepG2 cells were analyzed after 72 h of treatment with both drugs. Cell proliferation, cytotoxicity, cytokines, apoptosis, senescence, autophagy and oxidative stress were accessed. Ιt was demonstrated that the combination is more efficient than the single use of substances, because subtherapeutic doses of rapamycin, when associated to FBP become effective, reducing cell proliferation, through a significant increase in the production of tiobarbituric acid reactive substances (TBARS), suggesting that this might be the cause of death by apoptosis. According to these results, we believe that the association of both drugs may be a promising choice for the treatment of hepatocarcinoma.
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Elisa Feller Gonçalves
EF
da Silva
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Gabriele Catyana
GC
Krause
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Kelly Goulart
KG
Lima
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Gabriela Viegas
GV
Haute
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Leonardo
L
Pedrazza
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Fernanda Cristina
FC
Mesquita
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Bruno Souza
BS
Basso
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Anderson Catarina
AC
Velasquez
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Fernanda Bordignon
FB
Nunes
Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil.
Jarbas Rodrigues
JR
de Oliveira
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000008:administration & dosage*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage*
D000975:Antioxidants; D005609:Free Radicals; D006597:Fructose-Bisphosphatase; D020123:Sirolimus