%0 Journal Article
%T Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel
%A Anthony Stanislaus
%A Athirah Bakhtiar
%A Diyana Salleh
%A Snigdha Tiash
%A Tahereh Fatemian
%A Sharif Hossain
%A Toshihiro Akaike
%A Ezharul Chowdhury
%J Cancer Cell International
%D 2012
%I BioMed Central
%R 10.1186/1475-2867-12-30
%X Here we show that carbonate apatite-mediated delivery of siRNA against PLC-gamma-2 (PLCG2) and calmodulin 1 (CALM1) genes has led to the sensitization of a human cervical cancer cell line to doxorubicin- and paclitaxel depending on the dosage of the individual drug whereas no such enhancement in cell death was observed with cisplatin irrespective of the dosage following intracellular delivery of the siRNAs.Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.Genes are transcribed into mRNAs and subsequently translated into proteins to carry out the major functions within a cell and the mutations in certain genes leading to their suppression or overexpression are usually responsible for both acquired and genetic diseases. Delivery of functional gene(s) or gene-silencing element(s) could be the potential options in restoring the normal functions of the cell. RNA interference (RNAi) that can selectively silence mRNA expression in cell cytoplasm can be utilized to develop new drugs against target therapeutic genes [1-5]. RNAi can be harnessed for selective gene inhibition in two different routes: 1) cytoplasmic delivery of short interfering RNA (siRNA) for directly breaking down the specific mRNA and 2) nuclear delivery of gene expression cassettes to express a short hairpin RNA (shRNA) which is further processed by cellular machinery to siRNA in the cytoplasm [6]. However, siRNA, a synthetic RNA duplex of 21¨C23 nucleotides, is more advantageous than shRNA because of the difficulty in the construction of a shRNA expression system [6], and the requirement of the expression system to overcome the nuclear barrier for shRNA expression [7]. siRNA in the cytoplasm of the cells incorporates into a multiprotein RNA-induced silencing complex (RISC) and is unwound into single-stranded RNAs by Argonaute 2, a multifunctional protein within the RISC, forming antisense strand-associated RISC in or
%K Carbonate apatite
%K Nanoparticle
%K siRNA
%K PLC-gamma-2
%K Calmodulin 1
%K Cervical cancer
%K Cisplatin
%K Doxorubicin
%K Paclitaxel
%U http://www.cancerci.com/content/12/1/30