Title:An Efficient Suppression of EGFR and B-Raf mRNA Overexpression in the Lung of Benzo[a]pyrene-induced mice by Cationic Lipo-ATRA Nanoformulation
Volume: 19
Issue: 1
Author(s): Berlin Grace Viswanathan Mariammal*, David Wilson Devarajan, Siddikuzzaman, Viswanathan Singaram, Ragavi Ravichandran, Guruvayoorappan Chandrasekharan and Kathirvelan Chinnadurai
Affiliation:
- Department of Biotechnology, Karunya Institute of Technology and Sciences, Karunya Nagar, Coimbatore, 641114,
Tamil Nadu, India
Keywords:
Benzo[a]pyrene, BRaf, EGFR, lipo-ATRA, lung cancer, RT, qPCR.
Abstract:
Background: The molecular drug all-trans retinoic acid (ATRA) acts on cancer cells via
different molecular pathways, but its poor bioavailability in cancer cells limits its potency. Recently
few patents have been published for the development of liposome-based drug for enhanced action.
This study was, therefore, carried out to analyse the oncogene expressions in the lung tissue of benzo[
a]pyrene (B[a]P)-induced mice and compare between free ATRA and cationic liposome nanoformulation
(lipo-ATRA) treatments.
Objective: This study was designed to analyse the changes in the expression levels of epidermal
growth factor receptor (EGFR) and B-Raf in the lung tissues of B[a]P-induced mice during the cancer
development stage itself and to find the suppressive effect of free ATRA and lipo-ATRA.
Methods: Lung cancer was induced in mice by oral ingestion of 50mg/kg body weight B[a]P weekly
twice for four consecutive weeks. Then, the mice were treated with free and lipo-ATRA (0.60 mg/kg) for
30 days via i.v injection. The EGFR and B-Raf gene expressions were analyzed in lung cells by reverse
transcriptase polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR).
Results: The RT-PCR gene band density and the relative quantity (RQ) values from qPCR revealed
both EGFR and B-Raf genes to be significantly overexpressed in B[a]P control mice while having very
low or no expression in normal mice. This indicates that they function as oncogenes in B[a]P-induced
lung carcinogenesis. The lipo-ATRA treatment has shown a highly significant increase in RQ values
for both EGFR and BRaf when compared to the free ATRA treatment.
Conclusion: The study results have revealed the cationic lipo-ATRA treatment to have enhanced the
bioavailability of ATRA in lung tissue due to its significant suppression action on EGFR-mediated
oncogenes’ expressions. Furthermore, the EGFR and BRaf could be the molecular targets of ATRA
action in lung carcinogenesis.
