title: Kinesin spindle protein SiRNA slows tumor progression.
abstract: The kinesin spindle protein (KSP), a member of the kinesin superfamily of microtubule-based motors, plays a critical role in mitosis as it mediates centrosome separation and bipolar spindle assembly and maintenance. Inhibition of KSP function leads to cell cycle arrest at mitosis with the formation of monoastral microtubule arrays, and ultimately, to cell death. Several KSP inhibitors are currently being studied in clinical trials and provide new opportunities for the development of novel anticancer therapeutics. RNA interference (RNAi) may represent a powerful strategy to interfere with key molecular pathways involved in cancer. In this study, we have established an efficient method for intratumoral delivery of siRNA. We evaluated short interfering RNA (siRNA) duplexes targeting luciferase as surrogate marker or KSP sequence. To examine the potential feasibility of RNAi therapy, the siRNA was transfected into pre-established lesions by means of intratumor electro-transfer of RNA therapeutics (IERT). This technology allowed cell permeation of the nucleic acids and to efficiently knock down gene expression, albeit transiently. The KSP-specific siRNA drastically reduced outgrowth of subcutaneous melanoma and ovarian cancer lesions. Our results show that intratumoral electro-transfer of siRNA is feasible and KSP-specific siRNA may provide a novel strategy for therapeutic intervention.
authors.affiliation: Takis srl, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marra
authors.forename: Fabio
authors.initials: F
authors.lastname: Palombo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018274:Electroporation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008545:Melanoma; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000628:therapy*; D010051:Ovarian Neoplasms; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C470243:KIF11 protein, human; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C521052:Kif11 protein, mouse; D016547:Kinesins