The online version of this article (doi:10.1186/1475-2867-12-30) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
AS has originally planned the project in close discussion with EHC and TA and finally carried out the experiments in collaborations with MJC, APK and SH. All authors read and approved the final manuscript.
RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed to rapidly develop potential novel drugs against a complex disease like cancer. However, naked siRNA being anionic is unable to cross the anionic cell membrane through passive diffusion and therefore, delivery of siRNA remains a major hurdle to overcome before the potential of siRNA technology can fully be exploited in cancer. pH-sensitive carbonate apatite has recently been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis. Moreover, internalized siRNA was found to escape from the endosomes in a time-dependent manner and efficiently silence gene expression.
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.
Authors’ original file for figure 112935_2012_343_MOESM1_ESM.tiff
Authors’ original file for figure 212935_2012_343_MOESM2_ESM.tiff
Authors’ original file for figure 312935_2012_343_MOESM3_ESM.tiff
Authors’ original file for figure 412935_2012_343_MOESM4_ESM.tiff
Authors’ original file for figure 512935_2012_343_MOESM5_ESM.tiff
Authors’ original file for figure 612935_2012_343_MOESM6_ESM.tiff
Authors’ original file for figure 712935_2012_343_MOESM7_ESM.tiff
Lu PY, Xie F, Woodle MC: In vivo application of RNA interference: from functional genomics to therapeutics. Adv Genet. 2005, 54: 117-142. PubMed
Dickerson EB, Blackburn WH, Smith MH, Kapa LB, Lyon LA, McDonald JF: Chemosensitization of cancer cells by siRNA using targeted nanogel delivery. BMC Cancer. 2010, 10: 1-11. 10.1186/1471-2407-10-1. CrossRef
Brader S, Eccles SA: Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori. 2004, 90: 2-8. PubMed
Stanislaus A, Hossain S, Chua MJ, Kunnath AP, Wen QC, Syakira SN, Siong GY, Loong SW, Othman I, Akaike T, Chowdhury EH: Fabrication and intracellular delivery of siRNA/carbonate apatite nano-composites for effective knockdown of cyclin B1 gene. Drugs Therp Studies. 2011, 1: 26-30.
Li CJ, Heim R, Lu P, Pu Y, Tsien RY, Chang DC: Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique. J Cell Sci. 1999, 112: 1567-1577. PubMed
Eastman A: Activation of programmed cell death by anticancer agents: cisplatin as a model system. Cancer Cell. 1990, 2: 275-279.
Alberts DS, Garcia D, Mason-Liddil N: Cisplatin in advanced cancer of the cervix: an update. Semin Oncol. 1991, 18: 11-24. PubMed
- Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel
Ezharul Hoque Chowdhury
- BioMed Central
Neu im Fachgebiet Onkologie
e.Med Kampagnen-Visual, Mail Icon II