XIAP is highly expressed in esophageal cancer and its downregulation by RNAi sensitizes esophageal carcinoma cell lines to chemotherapeutics

Zhang, Shuguang; Ding, Fang; Luo, Aiping; Chen, Anguo; Yu, Zhengping; Ren, Shuhua; Liu, Zhihua; Zhang, Lin

doi:10.4161/cbt.6.6.4195

Cited by 46 publications

(43 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…XIAP siRNA enhances sensitivity to methotrexate in hepatoma (Chen et al, 2006), to cisplatin, fluorouracil and etoposide in oesophageal carcinoma (Zhang et al, 2007), to TRAIL in melanoma, breast cancer and pancreatic cancer (Chawla-Sarkar et al, 2004;McManus et al, 2004) and also sensitises pancreatic cancer cell lines to g-irradiation (Giagkousiklidis et al, 2007). The XIAP siRNA approach confirmed the validity of XIAP as a therapeutic target but the problem of in vivo delivery of siRNAs regimens still must be overcome.…”

Section: A549mentioning

confidence: 69%

A small molecule inhibitor of XIAP induces apoptosis and synergises with vinorelbine and cisplatin in NSCLC

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Evasion of apoptosis contributes to the pathogenesis of solid tumours including non-small cell lung cancer (NSCLC). Malignant cells resist apoptosis through over-expression of inhibitor of apoptosis proteins (IAPs), such as X-linked IAP (XIAP). METHODS: A phenylurea-based small molecule inhibitor of XIAP, XIAP antagonist compound (XAC) 1396-11, was investigated preclincally to determine its ability to sensitise to clinically relevant cytotoxics, potentially allowing dose reduction while maintaining therapeutic efficacy. RESULTS: XIAP protein expression was detected in six NSCLC cell lines examined. The cytotoxicity of XAC 1396-11 against cultured NSCLC cell lines in vitro was concentration-and time-dependent in both short-term and clonogenic assays. XAC 1396-11-induced apoptosis was confirmed by PARP cleavage and characteristic nuclear morphology. XAC 1396-11 synergised with vinorelbine±cisplatin in H460 and A549 NSCLC cells. The mechanism of synergy was enhanced apoptosis, shown by increased cleavage of caspase-3 and PARP and by the reversal of synergy by a pan-caspase inhibitor. Synergy between XAC 1396-11 and vinorelbine was augmented by optimising drug scheduling with superior effects when XAC 1396-11 was administered before vinorelbine. CONCLUSION: These preclinical data suggest that XIAP inhibition in combination with vinorelbine holds potential as a therapeutic strategy in NSCLC.

show abstract

Section: A549mentioning

confidence: 69%

A small molecule inhibitor of XIAP induces apoptosis and synergises with vinorelbine and cisplatin in NSCLC

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.2-79.1%), 16.7% (range 0.3-62.2%) and 4.6% (range 0-12.3%) respectively. These results were not significantly different compared to the control.…”

Section: Resultsmentioning

confidence: 99%

“…The association between upregulation of IAP family proteins, such as XIAP, cIAP-1, cIAP-2 and survivin, and an unfavorable course of disease has been confirmed in chronic lymphocytic leukemia [12]. Also, pathological overexpression of IAP family members has been observed in various solid tumors including prostate cancer, breast cancer, pancreatic cancer, gastric cancer and melanoma [13][14][15][16][17][18].…”

mentioning

confidence: 88%

Expression of IAP family proteins and its clinical importance in breast cancer patients

Pluta¹,

Jeziorski²,

Cebula-Obrzut³

et al. 2015

neo

View full text Add to dashboard Cite

Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (p<0.001) were seen among the expressions of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs. pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months respectively. No significant correlations were observed among expressions of IAP family proteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.

show abstract

“…Croci DO et al have shown that after siRNA transfection against survivin and down-regulation of survivin, translocation of the AIF from the cytoplasm to the nucleus occurs, which is a molecular indicator of the caspase-independent apoptosis of cells (Croci et al, 2008). Combined use of cisplatin, fluorouracil, paclitaxel, etoposide, and XIAP siRNA have been shown to result in better chemotherapeutic activity and to efficiently decrease XIAP expression and make it sensitive to cancer treatments (Zhang et al, 2007;Wei et al, 2008).…”

Section: Targeting Iapsmentioning

confidence: 99%

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

486

338

View full text Add to dashboard Cite

Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

show abstract

XIAP is highly expressed in esophageal cancer and its downregulation by RNAi sensitizes esophageal carcinoma cell lines to chemotherapeutics

Cited by 46 publications

References 26 publications

A small molecule inhibitor of XIAP induces apoptosis and synergises with vinorelbine and cisplatin in NSCLC

A small molecule inhibitor of XIAP induces apoptosis and synergises with vinorelbine and cisplatin in NSCLC

Expression of IAP family proteins and its clinical importance in breast cancer patients

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Contact Info

Product

Resources

About