No abstract

SG600-IL24 can selectively suppress the proliferation and apoptosis of HCC cell lines in vitro but not normal liver cell line L02 in a p53-independent manner. Compared with Ad.IL-24, SG600-IL24 can significantly enhance the antitumor activity in HCC cell lines.

Abstract. Heat shock protein 70 (HSP70), a chaperone involved in tumor progression, is overexpressed in various human tumors. However, its role in colon cancer progression is not completely understood. In the present study, two shRNA plasmid vectors against HSP70 were constructed and stably transfected into the colon cancer cell line HT29 to determine the effect of HSP70 on cell proliferation, cell cycle distribution and cell apoptosis in HT29 cells in vitro, and its effect on xenograft tumor growth and apoptosis in vivo. Cell proliferation was determined using MTT assay. The results revealed that HSP70 silencing efficiently inhibited the growth of HT29 cells in culture, induced cell cycle arrest at the G1 phase, and significantly increased apoptosis. Moreover, stable clones from the HSP70 shRNA-2 vector suppressed xenograft tumor growth and enhanced apoptosis in vivo compared with a mock and vector control group. In conclusion, specific HSP70 shRNA silencing may inhibit colon cancer growth, indicating that HSP70 silencing is a potential therapeutic strategy for the treatment of colon cancer. IntroductionColorectal carcinoma (CRC) is one of the most common malignant diseases in China. The incidence of colon cancer has been on the increase, becoming a major threat to public health. CRC is the third most frequently diagnosed cancer in the USA. In 2005, an estimated 105,950 new cases of colon cancer occurred. During the same year, an esti mated 55,290 individuals succumbed to CRC (1). Therefore, it is vital that early detection and treatment be improved, particularly the efficacy of treatment to reduce mortality and extend the lives of patients.Heat shock proteins (HSP), which are stress proteins acting as molecular chaperones, are generally induced by various environmental and pathophysiological stimuli (2). The protective function of HSP70 is related to its ability to promote folding of nascent polypeptides and to remove denatured proteins (3). However, HSP70 facilitates cancer cell survival and growth in various human tumor cells by inhibiting apoptosis and promoting proliferation (4,5). The specific expression of HSP70 acting as an anti-apoptotic chaperone protein is commonly higher in cancer cells including breast, colon (6), ovarian (6) and pancreatic cancers (7). An elevated expression of HSP70 correlates with increased tumor cell proliferation, invasion, migration and poor prognosis. Therefore, HSP70 has been proposed as a putative target for cancer treatment.RNA interference (RNAi), a genetic interference phenomenon that involves the post-transcriptional gene silencing mechanism, effectively suppresses the expression of a particular gene through the introduction of short interfering RNAs (8). However, the effect of down-regulated HSP70 expression by RNAi on colon cancer growth in vitro and in vivo has yet to be examined.In this study, two shRNA plasmid vectors against HSP70 were constructed and transfected into the colon cancer cell line HT29 using RNAi technology, which persistently generated siRNA inside...

At present, no satisfactory anti‐liver fibrosis drugs have been used clinically due to the poor targeting ability and short half‐life period. This study aimed to explore the effects of a new TRAIL ( TNF ‐related apoptosis‐inducing ligand) preparation that can target aHSC s (activated hepatic stellate cells) on liver fibrosis and explain the possible underlying mechanism. Using our self‐made drug carrier pPB ‐ SSL that specifically targets aHSC s, recombinant human TRAIL (rh TRAIL ) protein was embedded in (named as pPB ‐ SSL ‐ TRAIL ) and applied to treat liver fibrotic mice as well as 3T3 fibroblast cells and aHSC s. Through in vitro and in vivo experiments, we found that, compared with the groups treated with TRAIL (free rh TRAIL ) and SSL ‐ TRAIL (rh TRAIL capsulated within unmodified liposome), the group treated with pPB ‐ SSL ‐ TRAIL nanoparticles showed significantly lower cell viability and higher cell apoptosis in vitro. The targeting delivering system pPB ‐ SSL also significantly enhanced the anti‐fibrotic effect, apoptosis induction and long circulation of rh TRAIL . After the treatment with pPB ‐ SSL ‐ TRAIL , apoptosis of aHSC s was notably increased and hepatic fibrosis in mice was remarkably alleviated. In vitro, pPB ‐ SSL ‐ TRAIL nanoparticles were mainly transported and located on membrane or into cytoplasm, but the particles were distributed mainly in mouse fibrotic liver and most on the cell membrane of aHSC s. In conclusion, rh TRAIL carried by pPB ‐ SSL delivering system has prolonged circulation in blood, be able to target aHSC s specifically, and alleviate fibrosis both in vitro and in vivo. It presents promising prospect in the therapy of liver fibrosis, and it is worthwhile for us to develop it for clinical use.

No abstract