Limits...
Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

Zheng S, Chang S, Lu J, Chen Z, Xie L, Nie Y, He B, Zou S, Gu Z - PLoS ONE (2011)

Bottom Line: Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro.Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1.In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms.

Methodology/principal findings: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo.

Conclusions/significance: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

Show MeSH

Related in: MedlinePlus

Cell proliferation inhibitory effects of 9NC and 9NC-LP on HepG2, L02 and Hep3B cells in vitro.Cell proliferation of HepG2(A), L02(B) and Hep3B(C) cells was measured after exposure to compounds for 24–72 h. All assays were done in triplicate. The proliferation index is in comparison with untreated cells (*P<0.01, <$>\raster(60%)="rg1"<$>P<0.05 vs. control) (There no significant differences between cells treated with 4‰DMSO, Liposomes (free) and untreated cells. Data not shown).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3111480&req=5

pone-0021064-g002: Cell proliferation inhibitory effects of 9NC and 9NC-LP on HepG2, L02 and Hep3B cells in vitro.Cell proliferation of HepG2(A), L02(B) and Hep3B(C) cells was measured after exposure to compounds for 24–72 h. All assays were done in triplicate. The proliferation index is in comparison with untreated cells (*P<0.01, <$>\raster(60%)="rg1"<$>P<0.05 vs. control) (There no significant differences between cells treated with 4‰DMSO, Liposomes (free) and untreated cells. Data not shown).

Mentions: To further determine the effects of 9NC and 9NC-LP on cell proliferation, HepG2, Hep3B and L02 were subject to BrdU proliferation assay. The proliferation of all cell lines was suppressed after the treatment with 9NC and 9NC-LP. The antiproliferative effects of both drugs were dose- and time- dependent. As showed in Fig. 2 HepG2 cell line was more sensitive in both 9NC and 9NC-LP. The results are similar to that of the MTT assay.


Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

Zheng S, Chang S, Lu J, Chen Z, Xie L, Nie Y, He B, Zou S, Gu Z - PLoS ONE (2011)

Cell proliferation inhibitory effects of 9NC and 9NC-LP on HepG2, L02 and Hep3B cells in vitro.Cell proliferation of HepG2(A), L02(B) and Hep3B(C) cells was measured after exposure to compounds for 24–72 h. All assays were done in triplicate. The proliferation index is in comparison with untreated cells (*P<0.01, <$>\raster(60%)="rg1"<$>P<0.05 vs. control) (There no significant differences between cells treated with 4‰DMSO, Liposomes (free) and untreated cells. Data not shown).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111480&req=5

pone-0021064-g002: Cell proliferation inhibitory effects of 9NC and 9NC-LP on HepG2, L02 and Hep3B cells in vitro.Cell proliferation of HepG2(A), L02(B) and Hep3B(C) cells was measured after exposure to compounds for 24–72 h. All assays were done in triplicate. The proliferation index is in comparison with untreated cells (*P<0.01, <$>\raster(60%)="rg1"<$>P<0.05 vs. control) (There no significant differences between cells treated with 4‰DMSO, Liposomes (free) and untreated cells. Data not shown).
Mentions: To further determine the effects of 9NC and 9NC-LP on cell proliferation, HepG2, Hep3B and L02 were subject to BrdU proliferation assay. The proliferation of all cell lines was suppressed after the treatment with 9NC and 9NC-LP. The antiproliferative effects of both drugs were dose- and time- dependent. As showed in Fig. 2 HepG2 cell line was more sensitive in both 9NC and 9NC-LP. The results are similar to that of the MTT assay.

Bottom Line: Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro.Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1.In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms.

Methodology/principal findings: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo.

Conclusions/significance: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

Show MeSH
Related in: MedlinePlus