RETRACTED ARTICLE: The anti-osteosarcoma property of ailanthone through regulation of miR-126/VEGF-A axis

Abstract

Background: Despite the characters of the resistance of tumour of ailanthone (AIL) were found in various tumour cells, its effect on osteosarcoma is still unclear. Herein, we attempted to see the effects of AIL on an osteosarcoma cell line MG63. Methods: MG63 cells were treated by AIL, following which CCK-8 assay, BrdU assay, Transwell assay and Western blot were utilized to detect cell proliferation, migration, invasion and apoptosis. miR-126 expression in osteosarcoma tissues and cell lines was measured by qRT-PCR. Further, the target of miR-126 and the downstream signalling for AIL were studied. Results: Treating MG63 cells with 1.5 lM AIL for 24 h significantly suppressed proliferation, migration, invasion and induced apoptosis. Meanwhile, AIL inhibited PI3K/AKT pathway and up-regulated miR-126 expression. miR-126 of osteosarcoma tissues and cell lines was low expressed, as relative to paracancerous tissues and normal osteoblast. The anti-tumour effects of AIL were attenuated by miR-126 silencing. Further, VEGF-A was a target of miR-126. Conclusions: This study demonstrated that AIL was effective in inhibiting MG63 cells growth, migration and invasion. The anti-tumour properties may be via up-regulating miR-126 and thereby degradation of VEGF-A.

Ailanthone: A novel potential drug for treating human cancer (Review)

“…A number of studies have demonstrated that abnormal expression of miRNA (miR-27a, 95-3p, 195 and 133b) was associated with osteosarcoma growth, metastasis and prognosis ( 77 – 79 ). For example, Kong et al ( 47 ) revealed that different concentrations of AIL inhibited MG63 osteosarcoma cell viability (P<0.01 or P<0.001) and proliferation (P<0.01) compared with those in the control group by increasing the levels of miR-126. Furthermore, cell migration and invasion were also inhibited by AIL, whereas the rate of apoptosis was increased.…”

“…Furthermore, cell migration and invasion were also inhibited by AIL, whereas the rate of apoptosis was increased. Protein expression levels of cyclin D1 and Bcl-2 were decreased, while Bax, cleaved PARP and cleaved caspase-3 were increased following treatment of MG63 cells with AIL compared with untreated cells ( 47 ). In addition, PTEN protein expression levels were increased; however, PI3K and AKT phosphorylation levels were decreased ( 47 ).…”

Anticancer properties and mechanism of action of the quassinoid ailanthone

“…Interestingly, five independent recent studies have underlined the capacity of AIT to regulate specific microRNA (miR), which are short (18–25 nucleotides), noncoding RNAs that posttranscriptionally control the expression of target genes. As illustrated in Figure 5, AIT downregulates the oncogenic miRNA miR‐21 (P. Yang et al, 2018) and upregulates the tumor suppressor miRNAs miR‐126 (Kong et al, 2019), miR‐195 (Hou et al, 2019), miR‐449a (Y. Zhang et al, 2019), and miR‐148a (Gao et al, 2019). These independent studies are briefly presented (Table 2).…”

“…miR‐126 is viewed as a tumor suppressor, notably in digestive system cancers where it downregulates various oncogenes (Hu, Xiong, Chen, Zhu, & Zhou, 2019). AIT was found to upregulate miR‐126 in MG63 osteosarcoma cells and this effect was responsible for inhibition of cell growth, migration and invasion (Kong et al, 2019). The effects of AIT are similar to those observed upon transfection of miR‐126 in osteosarcoma cells, leading to inhibition of proliferation, migration, invasion, and epithelial to mesenchymal transition, through inactivation of JNK and JAK1/STAT3 pathways (Jiang, Zhang, Liu, Gu, & Wu, 2017).…”

“…The effects of AIT are similar to those observed upon transfection of miR‐126 in osteosarcoma cells, leading to inhibition of proliferation, migration, invasion, and epithelial to mesenchymal transition, through inactivation of JNK and JAK1/STAT3 pathways (Jiang, Zhang, Liu, Gu, & Wu, 2017). AIT suppressed the activation of PI3K/AKT pathway and upregulates miR‐126, leading to the degradation of its target ligand VEGF‐A (Kong et al, 2019). In breast cancer, miR‐126 has been shown to modulate angiogenesis by targeting VEGF‐A‐mRNA (Alhasan, 2019).…”