PTEN-Akt/mTOR Expression Level in A549 Lung Cancer Cells in Response to Cisplatin, Carotenoids, and their Combination http://www.doi.org/10.26538/tjnpr/v8i1.9

Abstract

The negative impacts of cisplatin often lead to undesirable side effects. Moreover, the issue of resistance has been recognized as a substantial hurdle in achieving effective therapeutic results. Multiple studies have emphasized the reliance of particular tumors, such as lung cancer, on the PI3K/Akt/mTOR pathway. Cisplatin is known to initiate Akt regulation in cancer cells, which ultimately makes these cells resistant to apoptosis. Despite the existence of specific inhibitors tailored to intervene in the PI3K/Akt/mTOR pathway, the continuously evolving epigenetic environment of this cascade plays a role in the development of resistance in cancer cells against these inhibitors. Antioxidants, exemplified by carotenoids, have garnered attention due to their versatile roles. They function as pro-oxidants, initiating apoptosis in cancer cells, while also acting as antioxidants that promote the restoration of normal cell function. This study aimed to examine the influence of bixin and fucoxanthin, both separately and in conjunction with cisplatin, on the transcriptional levels of PTEN, Akt/mTOR, and the tumor suppressor p53 in A549 cell lines. Cell viability was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Drug combinations were performed in accordance with the Chou-Talalay theorem. The Real-Time Quantitative-Polymerase Chain Reaction (RT-q-PCR) method was employed to evaluate the expression levels of the PI3K/Akt/mTOR genes. The ongoing study furnished proof that carotenoids, particularly bixin and fucoxanthin, showcase anticancer attributes and have the potential to complement cisplatin chemotherapy in lung cancer cells. This potential is realized by influencing the modulation of PTEN and the decrease in Akt and mTOR expression.