The use of toxins for
cancer therapy has great promise.
Gelonin, a potent plant toxin, causes cell death by inactivating the 60S ribosomal subunit. Recently, we developed a novel gene delivery system using biodegradable cationic
heparin-
polyethyleneimine (HPEI)
nanogels. In the current study, the antitumor activity of a recombinant plasmid expressing
gelonin (pGelonin) on human
ovarian cancer was assessed. The application of HPEI
nanogels, was also evaluated.
Gelonin-
cDNA was cloned into the pVAX1 plasmid vector and transfected into SKOV3 human
ovarian cancer cells using biodegradable cationic HPEI
nanogels. The expression of
gelonin in vitro and in vivo was confirmed using RT-PCR and western blot analysis. Cell viability and apoptosis were examined using an MTT assay and flow cytometric analysis. For the in vivo study, an SKOV3 intraperitoneal ovarian
carcinomatosis model was established, and nude mice were randomly assigned into four groups receiving i.p. administration of pGelonin/HPEI complexes, pVAX/HPEI complexes, HPEI alone and 5%
glucose solution. The
tumor weight was monitored, and a TUNEL assay and Ki-67 immunohistochemistry were performed to evaluate apoptosis and cell proliferation in the
tumor tissue sections, respectively.
Gelonin was efficiently expressed in SKOV3
cancer cells in vitro and in vivo using pGelonin incorporated with HPEI
nanogels. The pGelonin/HPEI complexes inhibited cell viability and induced apoptosis in the cell culture. Treatment for intraperitoneal
carcinomatosis with pGelonin/HPEI complexes reduced the
tumor weight by ~58.55% compared to the control groups (P<0.05). The antitumor effect was accompanied by increased apoptosis and reduced cell proliferation (P<0.05). No significant side effects were observed with i.p. administration of the pGelonin/HPEI complexes. Our data indicate that HPEI
nanogel-delivered pGelonin may have promising applications against human
ovarian cancer.