Asiatic acid re-sensitizes multidrug-resistant A549/DDP cells to cisplatin by down regulating long non-coding RNA metastasis associated lung adenocarcinoma transcript 1/β-catenin signaling

Abstract

Drug resistance becomes a challenge in the therapeutic management of non-small cell lung cancer (NSCLC). According to our former research, asiatic acid (AA) re-sensitized A549/DDP cells to cisplatin (DDP) through decreasing multidrug resistance protein 1 (MDR1) expression level. However, the relevant underlying mechanisms are still unclear. Long non-coding RNA (lncRNA) MALAT1 shows close association with chemo-resistance. As reported in this research, AA increased apoptosis rate, down regulated the expression of MALAT1, p300, β-catenin, and MDR1, up regulated the expression of miR-1297, and decreased β-catenin nuclear translocation in A549/DDP cells. MALAT1 knockdown expression abolished the drug resistance of A549/DDP cells and increased cell apoptosis. MALAT1 could potentially produce interactions with miR-1297, which targeted to degradation of p300. In addition, p300 overexpression effectively rescued the effects of MALAT1 knockdown expression on A549/DDP cells and activate the expression of β-catenin/MDR1 signaling, and these could be effectively blocked by AA treatment. Conclusively, AA could re-sensitize A549/DDP cells to DDP through down-regulating MALAT1/miR-1297/p300/β-catenin signaling.

Crosstalk between lncRNAs and Wnt/β-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response

“…In A549/DDP cells, up-regulated expression of MALAT1 was linked to drug resistance thought β-catenin/MDR1 signaling. MALAT1 boosted drug resistance in A549/DDP cells via regulating β-catenin/MDR1 signaling via the miR- 1297/p300 axis [ 42 ]. Also miR-1297 had comparable effects in numerous experiments by regulating different signaling pathways.…”

The significance of the crosstalk between ubiquitination or deubiquitination and ncRNAs in non-small cell lung cancer

“…Therefore, through inhibiting MALAT1/miR-1297/p300/β-catenin/Wnt signaling, the A549/DDP cells were re-sensitized. Asiatic acid can achieve this regulation ( 43 ). Similarly, the MALAT1/miR-27a-5p/PBOV1 axis was recently found to enhance gemcitabine resistance in NSCLC cells ( 44 ).…”

Asiatic acid inhibits rheumatoid arthritis fibroblast‐like synoviocyte growth through the Nrf2/HO‐1/NF‐κB signaling pathway

“…It has the ability to modulate pro-inflammatory cytokines and slow down the progression of immuno-inflammatory diseases, and in vitro experiments have further demonstrated that AA can exert a protective effect through the inhibition of NF-κB activity (Jiang, Xu, Lu, Chen, & Li, 2022;Mioc et al, 2022). Recently, it has also been reported that AA can not only promote apoptosis of tumor cells with little toxicity and side effects, but also confirmed in lung and breast cancer cell models that AA can inhibit tumor growth and has no significant effect on normal cells (Cheng, Zhang, Zhong, Chen, & Peng, 2022;Gou et al, 2020). AA can also resist cisplatininduced acute kidney injury and does not affect normal cells (Yang et al, 2018).…”