Cited by 20RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryCancer-related Molecular Pathways

Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel

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Stanislaus, Anthony, Bakhtiar, Athirah, Salleh, Diyana, Tiash, Snigdha, Fatemian, Tahereh, Hossain, Sharif, Akaike, Toshihiro, Chowdhury, Ezharul Hoque·2012·Cancer Cell International

Abstract

Background: 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. Results: 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. Conclusion: Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.

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  • In human cervical adenocarcinoma cells, in vitro siRNA knockdown of PLCγ2 and calmodulin 1 led to increased sensitivity to doxorubicin and paclitaxel, but not Cisplatin.

    “PLCγ2 was also implicated in cervical adenocarcinoma, where in vitro siRNA knockdown of PLCγ2, and calmodulin 1, in human cervical adenocarcinoma cells led to an increased sensitivity to doxorubicin and paclitaxel, but not Cisplatin (147).”

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Authors
Stanislaus, A., Bakhtiar, A., Salleh, D., Tiash, S., Fatemian, T., Hossain, S., Akaike, T., & Chowdhury, E. H.
Affiliations
  • Monash University Malaysia (MY)
  • IMU University (MY)
  • Tokyo Institute of Technology (JP)
Corresponding author
Chowdhury, Ezharul Hoque
Venue
Cancer Cell International
Published
2012-06-18
Volume
12
Issue
1
Pages
30-30
ISSN
1475-2867 (ISSN-L)
OpenAlex
W2097214456
Cited by
20
References
35
Citations by year
2026: 3 · 2021: 5 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cancer Cell International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Greater South Information System
Funders
  • Kementerian Sains, Teknologi dan Inovasi
  • Ministério da Ciência, Tecnologia e Inovação
  • Japan Society for the Promotion of Science
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
cervical adenocarcinoma, doxorubicin, paclitaxel, cisplatin, chemosensitization, siRNA delivery, carbonated hydroxyapatite, pH-responsive nanoparticles, gene knockdown, RNA interference, drug resistance

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