Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin

Yang, Qian; Xia, Peng; Zhang, Sam; S, Pan; Zhao, Jianwu

doi:10.3892/or.2014.3698

Cited by 20 publications

(17 citation statements)

References 36 publications

(46 reference statements)

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“…Real-time PCR was performed using SYbR Premix Ex Taq (Takara, Dalian, China) under the 7900 Real-Time PCR system. Primers for XIAP and GAPDH were used as previously described (18). The fold-change in target mRNA or miRNA expression was calculated using the 2 -ΔΔCt method following normalization to GAPDH or U6 expression, respectively.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein

et al. 2016

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MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein

et al. 2016

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“…The release of Smac/Diablo in the cytosol also blocked the anti-apoptotic activity of XIAP by preventing it from binding to caspase-3 (8). XIAP also confers resistance to other anti-tumor agents such as TRAIL, doxorubicin and cisplatin (6,28). Additionally, XIAP has also been implicated in the process of metastasis, making it a viable potential target for cancer therapy (29).…”

Section: Discussionmentioning

confidence: 99%

Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells

et al. 2018

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5-fluorouracil (5-FU) has been used in the treatment of colorectal cancer for >50 years. However, drug resistance remains an obstacle in the application of 5-FU-based chemotherapy. Bufalin, a type of steroid with anti-tumor activity, may be purified from the skin and parotid venom glands of toads. In order to improve the anti-tumor effect of 5-FU, the present study examined the combined effects of bufalin with 5-FU on human colorectal cancer HCT116 cells. Following treatment, cell proliferation was quantified using MTT assay and apoptotic cell percentage was assessed by flow cytometry. The apoptosis-associated protein expression was evaluated by western blotting. It was observed that bufalin enhanced the cytotoxicity of 5-FU in HCT116 cells via the induction of the mitochondrial apoptotic pathway. Additionally, bufalin combined with 5-FU reduced the expression levels of anti-apoptotic proteins, such as Mcl-1, XIAP and Bcl-2 and upregulated the levels of the pro-apoptotic proteins, Bax and Bad. To verify the role of Bax, RNA interference was used to knock-down Bax. It was determined that the synergistic effect between 5-FU and bufalin was diminished following the silencing of Bax. In summary, bufalin in combination with 5-FU may induce a higher level of apoptosis compared with monotherapy, and the combination mat be a potential therapeutic strategy for the treatment of colorectal cancer.

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“…Given its role in accelerating apoptosis, we predicted that the target genes would be anti-apoptotic. Scores of studies have confirmed the tight connection between proteins of the IAP family and BCL2 family with carcinogenesis, including studies of ovarian cancer (9,15,(44)(45)(46). We hypothesized that miR-146a-5p could possibly regulate these two families, by decreasing expression of these proteins which are often overexpressed in chemoresistant EOC cells.…”

Section: Screening Of Anti-apoptotic Genes Targeted By Mir-146a-5pmentioning

confidence: 94%

MicroRNA-146a-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes

Jin

et al. 2017

International Journal of Oncology

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MicroRNAs play a crucial role in gene expression regulation in various types of cancers. Previous studies show the expression level of miR‑146a‑5p is downregulated in epithelial ovarian cancer. Further investigations suggest this downregulation is responsible for apoptosis resistance in ovarian cancer cells. However, the mechanism of how miR‑146a‑5p promotes apoptosis remains unclear. In this study, the role of miR‑146a‑5p in cisplatin‑induced apoptosis of ovarian cancer cells was assessed by DAPI staining, MTT assays, and monitoring expression of XIAP, BCL2L2, BIRC2 and BIRC5 through a dual‑luciferase assay. Our results show that miR‑146a‑5p can regulate three important anti‑apoptotic genes including XIAP, BCL2L2 and BIRC5 via their 3'UTRs. Not only can overexpression of miR‑146a‑5p downregulate the expression of XIAP in SKOV3 cells, but it also lowers the IC50 values of cisplatin in OVCAR3 and SKOV3 cells and enhances the susceptibility of OVCAR3, SKOV3 and primary ovarian cancer cells to cisplatin‑induced apoptosis. The effect of XIAP rescuing cisplatin‑induced apoptosis accelerated by miR‑146a‑5p further supports our conclusion. Our results suggest that the regulation of three anti‑apoptotic genes by miR‑146‑5p enhances the therapeutic effects of cisplatin.

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Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin

Cited by 20 publications

References 36 publications

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein

Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells

MicroRNA-146a-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes

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