Abstract
BackgroundThirty to 40 % of non-small cell lung cancer (NSCLC) patients developed higher hypertriglyceridemia in the process of treatment with bexarotene. And bioinformatics studies discovered that the expression of slc10a2 was increased in high-grade hypertriglyceridemia patients. So, we will explore the mechanism which may involve in this process.MethodsWe constructed slc10a2 overexpressed A549 cells and H1299 cells as cell models, normal A549 cells and H1299 cells as control. Then we explored the effects of slc10a2 on A549 cells and H1299 cells behaviors, including proliferation, invasion and apoptosis. The expression of apoptotic related genes and anti-cancer genes also been detected.ResultsWe found that the proliferation and migration were inhibited and the apoptosis of NSCLC cells was accelerated by bexarotene. In addition, overexpressed slc10a2 in NSCLC cells can further suppress the proliferation and migration, and promote apoptosis under the treatment of bexarotene. On the contrary, the opposite results were obtained after slc10a2 gene was silenced in NSCLC cells treated with bexarotene. Moreover, the expression of caspase 3, caspase 7, PTEN, P21, P53, LKB1, TSC2 were increased and the expression of Bcl-2, cyclin D1, c-FLIP were declined in NSCLC cells and slc10a2 overexpressed NSCLC cells with the treatment of bexarotene, and the opposite situations were seen after slc10a2 gene was silenced in NSCLC cells. The further studies revealed the increased expression of slc10a2 activated the expression of peroxisome proliferator-activated receptor γ (PPARγ), then up-regulated PTEN expression and down-regulated mTOR expression.ConclusionThese results suggest that bexarotene inhibits the viability of lung cancer cells via slc10a2/PPARγ/PTEN/mTOR signaling pathway.
Highlights
Thirty to 40 % of non-small cell lung cancer (NSCLC) patients developed higher hypertriglyceridemia in the process of treatment with bexarotene
We found that the expression of anti-apoptotic proteins Bcl-2, cyclin D1 and c-FLIP was reduced whereas the expression of apoptotic proteins caspase-3, caspase-7 and tumor suppressor gene PTEN, P21, P53, LKB1, TSC2 were accelerated in A549 cells with the treatment of bexarotene, which was associated with the activation of peroxisome proliferator-activated receptor γ (PPARγ) through enhancing the expression of slc10a2, resulting in promoting the apoptosis of A549 cells
We demonstrated that this effects owned to the increased expression of PPARγ via enhancing the expression of slc10a2, up-regulated the expression of PTEN and down-regulated the expression of mTOR, increased the expression of apoptotic genes and anti-cancer genes, and reduced the expression of anti-apoptotic genes to suppress the proliferation of NSCLC cells and promote the apoptosis of NSCLC cells [34]
Summary
Thirty to 40 % of non-small cell lung cancer (NSCLC) patients developed higher hypertriglyceridemia in the process of treatment with bexarotene. Bexarotene (Scheme 1) is a synthetic retinoid modulator of retinoid X receptors (RXRs), it can selectively bind and activate RXRs [2], which include (RXRα, RXRβ, and RXRγ) [7], and play a critical role in cellular growth modulation, activation of apoptosis, induction of differentiation. It has been widely explored as potential target for cancer therapies for several years [8, 9].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
