XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway

Abstract

The present study assessed the effects of the tankyrase (TNKS) small molecule inhibitor XAV939 on the proliferation and migration of lung adenocarcinoma A549 cells and the possible underlying mechanism. To do this, the association between TNKS and the WNT/β-catenin signaling pathway in lung acinar adenocarcinoma was investigated. Immunohistochemistry was performed, which demonstrated that TNKS, β-catenin and Myc proto-oncogene protein (c-Myc) proteins are positively expressed in lung adenocarcinoma tissue; this expression was significantly higher than that in normal adjacent non-carcinoma tissues. A549 cell proliferation was inhibited in all XAV939-intervention groups examined. In the wound-healing assay, cells treated with different concentrations of XAV939 exhibited a significantly increased scratch width compared with the control group. Reverse transcription-semi-quantitative polymerase chain reaction analysis revealed that β-catenin mRNA expression was significantly decreased in A549 cells in response to different XAV939 concentrations compared with the control group. Immunofluorescence revealed that β-catenin protein, initially localized in the nucleus/cytoplasm, gradually translocated to the cytoplasm/membrane, an effect that was associated with increased drug concentration. TNKS, β-catenin and c-Myc protein expression in A549 cells treated with XAV939 was reduced compared with that in untreated cells. Therefore, abnormally high TNKS expression may promote the occurrence of lung cancer. The TNKS inhibitor XAV939 inhibited lung adenocarcinoma A549 cell proliferation and migration in vitro. The underlying mechanism by which XAV939 exerted its inhibitory effects may be associated with attenuation of the WNT signaling pathway.

<p>GOLPH3 Promotes Angiogenesis of Lung Adenocarcinoma by Regulating the Wnt/β-Catenin Signaling Pathway</p>

“…18 Previous studies have shown that cisplatin could show efficacy in a variety of solid tumors, for example, ovarian cancer, 19 prostate cancer, testicular cancer 20 and lung cancer. 21 In our study, cisplatin was found to reduce the activities of LADC, A549 and H23 cells, and the expression of GOLPH3 was also significantly reduced. To further investigate the role of GOLPH3 in anticancer effect of cisplatin, knocking out or overexpressing the GOLPH3 plasmid into A549 and H23 cells showed that silencing GOLPH3 could further inhibit cell viability, compared to cisplatin-treated cancer cells, and that the phosphorylation level of Akt protein was significantly reduced.…”

Effect of sitagliptin on tubulointerstitial Wnt/β‐catenin signalling in diabetic nephropathy

“…33 XAV939 is a selective small-molecule inhibitor of Wnt/β-catenin signaling. 34 In addition, the in vitro cell cultures indicated that XAV939 and sitagliptin intervention inhibit high glucoseinduced hyperexpression of Wnt4 and β-catenin, downregulate α-SMA expression, and partially restore E-cadherin biological activity. Our in vivo studies also demonstrated that sitagliptin can ameliorate renal functional and structural damage by reducing the hyperexpression of Wnt4 and β-catenin and inhibiting transdifferentiation in the tubulointerstitium.…”

Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer

“…We treated A549 cells (1,2,4,8,16,32,64, and 128 M), M2-like TAMs (1, 2, 4, 5, and 8 M), and ex vivo TAMs from human and mouse lung tumors with XAV939 (5 M; Tocris, Wiesbaden-Nordenstadt, Germany) and M2-like TAMs with RS 504393 (5 M; Tocris, Wiesbaden-Nordenstadt, Germany) as per the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay protocol and a previous study (40) for 24 hours at 37°C.…”