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2011
Conference Paper
Title
The variations in the BCL2 genes expression in lung cancer cells after exposure to erlotinib and gefitinib
Abstract
Introduction: The BCL2 family proteins are apoptotic regulators which play an important role in cancer cell survival. These proteins are also associated with resistance to anticancer drugs. Erlotinib and gefitinib are tyrosin kinase inhibitors which are used in the treatment of lung cancer. This study investigated the differences in the BCL2 gene expression after treatment of resistant or sensitive lung cancer cell lines with gefitinib and erlotinib.
Methodology: Real time PCR was performed after RNA isolation 24h after exposing the cells to the drugs. Resistant cell lines H1299 and A549 were compared to the sensitive HCC827 as well as a resistant HCC827. Resistant cells were established by long term exposure to erlotinib and gefitinib.
Results: 8 genes were investigated which were selected randomly considering both pro-apoptotic and anti-apoptotic regulators. Anti-apoptotic were: BCl2-XL, BCL2 α and MCL1-L, pro-apoptotic included MCL2-S, BIK; BIM γ, BIM-EL and BAD, EEF2 was used as the reference gene. The gene expression varied in all the cell lines. BCL2-XL, MCL1-S and BIM were surpressed by erlotininb where as only BIM γ was suppressed by gefitinib in all cell lines. Apart from, BCL2 α and BIM-EL al other genes did not show a significant difference to the control. BCL2 α was highly expressed in HCC827 whereas BIM EL was highly expressed in HCC827 and A549.
Conclusion: Since BCL2 α is an anti-apoptotic protein, its increased expression after treatment of HCC827 cell line can be associated with resistance to TKI. BIM EL on the other hand mediates the intrinsic apoptotic pathway when TKI are applied.
Methodology: Real time PCR was performed after RNA isolation 24h after exposing the cells to the drugs. Resistant cell lines H1299 and A549 were compared to the sensitive HCC827 as well as a resistant HCC827. Resistant cells were established by long term exposure to erlotinib and gefitinib.
Results: 8 genes were investigated which were selected randomly considering both pro-apoptotic and anti-apoptotic regulators. Anti-apoptotic were: BCl2-XL, BCL2 α and MCL1-L, pro-apoptotic included MCL2-S, BIK; BIM γ, BIM-EL and BAD, EEF2 was used as the reference gene. The gene expression varied in all the cell lines. BCL2-XL, MCL1-S and BIM were surpressed by erlotininb where as only BIM γ was suppressed by gefitinib in all cell lines. Apart from, BCL2 α and BIM-EL al other genes did not show a significant difference to the control. BCL2 α was highly expressed in HCC827 whereas BIM EL was highly expressed in HCC827 and A549.
Conclusion: Since BCL2 α is an anti-apoptotic protein, its increased expression after treatment of HCC827 cell line can be associated with resistance to TKI. BIM EL on the other hand mediates the intrinsic apoptotic pathway when TKI are applied.
Conference