Efficient inhibition of intraperitoneal human ovarian cancer growth by short hairpin RNA targeting CD44.
CD44 is one member of a big glycoprotein family involved in adhesion of cells or cells and extracellular matrix (ECM). The heavily glycosylated CD44 has been proved to be a major receptor of hyaluronan and a marker of stem cells in ovarian cancer. Here, using short hairpin (shRNA) against CD44, we demonstrate that knockdown CD44 could inhibit cancer growth efficiently compared with controls. Plasmid targeting CD44 gene (pshCD44) or non-relative control sequences (pshHK) was constructed and delivered to ovarian cancer by biodegradable poly D, L-Lactide-co-glycolide acid nanoparticles (PLGANPs). Nude mice were utilized in an intraperitoneal model of ovarian carcinomatosis to assess antitumor efficacy in vivo. Antitumor efficacy was estimated by changes in tumor weights, proliferation (Ki-67), apoptosis (TUNEL) and angiogenesis (CD31 staining and alginate-encapsulated tumor beads assay) in tumor cells. As results, pshCD44 or pshHK could be effectively transfected into SKOV-3 cells by PLGANPs. Tumor weight in pshCD44/PLGANPs group was suppressed by 45% and 50% compared with those in pshHK/PLGANPs and untreated group, respectively (Ps < 0.001). Inhibition of cell proliferation, induction of apoptosis and reduction of angiogenesis in tumor cells of pshCD44/PLGANPs group also show significant difference compared with those in control groups (Ps < 0.05), respectively. These results indicate that pshCD44 delivered by PLGANPs might be a potential approach in ovarian cancer therapy, and point towards a mechanism involving the inhibition of angiogenesis, cellular proliferation and the induction of apoptosis.
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Zou
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Yi
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Song
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Li
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Wei
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Zhao
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000502:physiology; D019344:Lactic Acid / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000235:genetics*
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid