ABSTRACT
AIM: All Trans Retinoic acid (ATRA) is an efficient drug for leukemia, but is not efficient therapy for solid cancers. Hence we have used 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol lipo-ATRA to investigate its molecular therapeutic effect on lung cancer. The objective was to find whether it could enhance ATRA receptor, RAR-ß expression in lung cells as it was lost in majority of cancers including lung cancer. MATERIALS AND METHODS: The study was made in an experimental C57BL/6 mice model developed by tail vein injection of B16F10 cells and in A549 human lung cancer cells. The RAR-ß protein expression was studied by Immunohistochemistry/Immunocytochemistry and the mRNA expression was studied by RT-PCR and qPCR methods. KEY FINDINGS: Both free and lipo-ATRA treatments showed an enhancement of RAR-ß protein and gene expressions, indicating its induction on RAR ß. However, lipo-ATRA treatment has shown significant induction when compared with free ATRA treatment. SIGNIFICANCE: Our results implies that the DSPC lipo-ATRA treatment might have accumulated more ATRA in to the target cells which might have resulted in the induction of its receptor RAR-ß expression in a hypothesis of ligand induced receptor expression.
Subject(s)
Antineoplastic Agents/administration & dosage , Lung Neoplasms/drug therapy , Melanoma, Experimental/drug therapy , Phosphatidylcholines/chemistry , Tretinoin/administration & dosage , A549 Cells , Animals , Antineoplastic Agents/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/pathology , Male , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , RNA, Messenger/metabolism , Receptors, Retinoic Acid/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tretinoin/pharmacologyABSTRACT
BACKGROUND: The high mortality rate of lung cancer is highly associated with faster metastasis spread. All Trans Retinoic Acid (ATRA), being the first choice drug for leukemia therapy is now under intense study for its therapeutic efficiency in other solid cancers. OBJECTIVES: This study was aimed to investigate the anti-metastasis activity of free ATRA and liposome entrapped ATRA (5:4:1) in the experimental C57BL/6 mice model developed by the injection of B16F10 cell line into the tail vein. METHOD: The ATRA drug was given via i.p for 21 days. The visual lung and liver metastatic tumor nodules were noted. Various biochemical markers of cancer metastasis in the serum as well as tissues were also analyzed after sacrifice. RESULTS: Tumor nodules have significantly decreased in ATRA treatment groups (32.83 ± 1.83 for free ATRA, 23 ± 2.36 for DSPC Lipo-ATRA) when compared with metastasis control (63.16 ± 2.9) in the lungs. Among the treatment groups, the DSPC lipo-ATRA treated group showed a significant tumor growth inhibition (63.6%) than that of in the free ATRA treated groups (48%). Similar anti-metastatic effect was observed in liver also. Furthermore lipo-ATRA has shown a significant change in the levels of biochemical cancer markers analyzed in this study. CONCLUSION: Our results concluded that the liposome encapsulated ATRA has an enhanced anti-metastasis potency than the free ATRA during B16F10 metastatic cell line implantation.
