Anti-tumor Activity of Adriamycin-loaded Chitosan Nanoparticles Surface-modified with Glycyrrhizin on Human Hepatoma Cell Line SMMC-7721 / 中国药房

OBJECTIVE: To investigate the anti-tumor activity of adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin on human hepatoma cell line SMMC-7721. METHODS: Inhibition effect of drug-loaded nanoparticle on the proliferation of SMMC-7721 cells was determined with MTT method. Intra-cellular distribution of nanoparticles and morphological change of SMMC-7721 cells before and after treatment were observed by confocal laser scanning microscope (CLSM) and the apoptosis induced by adriamycin was measured by TUNEL assay. RESULTS: The inhibition effect of adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin on the proliferation of SMMC-7721 cells increased 6.36 times lower in comparison with free drugs. The inhibition effect of adriamycin-loaded chitosan nanoparticles had no obvious improvement. Nanoparticles surface-modified with glycyrrhizin promoted the distrubition of adriamycin in the nucleus, so as to promote the anti-tumor activity of adriamycin. TUNEL assay indicated that nanoparticles surface-modified with glycyrrhizin induce DNA fragmentation and nucleus breakdown to induce the apoptosis of SMMC-7721 cells. CONCLUSION: Adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin can used as potential active hepatocyte-targeted delivery carrier. Pharmacokinetic evaluation of it is worthy of further studing.

Periplocin of cortex periplocae inhibits Stat3 signaling and induces apoptosis in human hepatocellular carcinoma cell line SMMC-7721 / 第三军医大学学报

Objective To investigate the effect of periplocin of cortex periplocae (CPP) on Stat3 signaling and its probable molecular mechanism of inducing apoptosis and anti-tumor activity. Methods Cell proliferation was detected by MTT. Cell apoptosis and cell cycle were investigated by flow cytometry. Expression of Stat3 protein in SMMC-7721 cells was analyzed by Western blot. Mcl-1, Survivin and XIAP mRNA expressions were measured by RT-PCR. Results CPP inhibited the proliferation of SMMC-7721 cells significantly, induced their apoptosis and arrested their cell cycle at G2/M phase. Decreased expression of Stat3 protein in the cell nucleus was observed after CPP treatment, but no significant changes were found in cytoplasma. Mcl-1, Survivin and XIAP mRNA expression levels were decreased in a time-dependent manner. Conclusion CPP inhibits cell proliferation and induces apoptosis by inhibiting Stat3 signal transduction in human hepatocellular carcinoma cell line SMMC-7721.

siRNA targeting STAT5 induces apoptosis in human hepatocellular carcinoma cell line SMMC-7721 / 第三军医大学学报

Objective To investigate the effects of inhibition of STAT5 gene expression by RNA interference technology on apoptosis of human hepatocellular carcinoma cell line SMMC-7721. Methods Three siRNA eukaryotic expression vectors against STAT5 were constructed and transfected with lipofectamineTM 2000 into SMMC-7721 cells. The changes in STAT5 expression were detected by semi-quantitative RT-PCR and Western blot. Cell apoptosis was assayed by flow cytometry (FCM). Results The sequence-specific siRNA could effectively and specifically inhibit STAT5 gene expression at both mRNA and protein levels. The inhibition rates of STAT5 mRNA expression were 70.43%, 43.02%, and 45.07%, respectively. The inhibition rates of STAT5 protein expression were 67.45%, 37.36%, and 41.86%, respectively. At 48 h after transfection, apoptosis rate was 25.61%. Conclusion siRNA against STAT5 can inhibit STAT5 gene expression in SMMC-7721 cells effectively and specifically and induce apoptosis of SMMC-7721 cells. siRNA targeting STAT5 has a great potential value in gene therapy of hepatocellular carcinoma.