The antitumor effect of folic acid conjugated-Auricularia auricular polysaccharide-cisplatin complex on cervical carcinoma cells in nude mice

Int J Biol Macromol. 2018 Feb;107(Pt B):2180-2189. doi: 10.1016/j.ijbiomac.2017.10.087. Epub 2017 Nov 11.

Abstract

A tumor-targeted, folic acid (FA) conjugated-Auricularia auricular polysaccharide (AAP) -cis-diaminedichloroplatinum (CDDP) complex (FA-AAP-CDDP) was used for cervical carcinoma chemotherapy. The drug delivery system was able to enhance the antitumor potency of CDDP, and to reduce the toxic side effects of CDDP. The kidney of mice treated by FA-AAP-CDDP complex had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and lower malondialdehyde. FA-AAP-CDDP complex could induce more interleukin-2, interleukin-4, and interferon-γ in mice. In addition, the FA-AAP-CDDP complex significantly promoted the expression of Bax and caspase-3 protein, but inhibited the expression of Bcl-2 protein, which activated the mitochondrial apoptotic pathway of tumor cells in nude mice. Moreover, the FA-AAP-CDDP complex had a higher intratumoral accumulation, was lower in the kidneys. This study may provide a new direction for folate receptor targeted polymers to improve anti-tumor activity, but reduce side effects of CDDP.

Keywords: Cisplatin; Folate receptors; Folic acid; Nude mice; Tumor cells.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Basidiomycota / chemistry*
  • Body Weight
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Creatinine / metabolism
  • Cytokines / blood
  • Female
  • Folic Acid / pharmacology
  • Folic Acid / therapeutic use*
  • Kidney / drug effects
  • Kidney / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nitrogen / metabolism
  • Organ Specificity
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Urea / metabolism
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Cytokines
  • Polysaccharides
  • Urea
  • Folic Acid
  • Creatinine
  • Nitrogen
  • Cisplatin