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2000
Volume 19, Issue 1
  • ISSN: 1872-2105
  • E-ISSN: 2212-4020

Abstract

Background

The molecular drug all-trans retinoic acid (ATRA) acts on cancer cells 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 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.

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2023-11-01
2024-12-25
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  • Article Type:
    Research Article
Keyword(s): Benzo[a]pyrene; BRaf; EGFR; lipo-ATRA; lung cancer; qPCR; RT
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