CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53

Zhang, Yafei; Li, Xiaohua; Shi, Yongquan; Wu, Yingyi; Li, Ning; He, Qiang; Ji, Qing; Wang, Rongquan; Yang, Shiming; Fang, Dian‐Chun

doi:10.3892/or.2011.1148

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Therefore we assumed that CIAPIN1 gene may up-regulate MDR1 expression by regulating wild-type P53 expression, which leads to breast cancer cell resistance. Meanwhile we must emphasize that in our study we selected MCF7/ADM and its parental MCF7 cell line as targets, and whether this conclusion still holds for other breast cancer cell lines still needs further study [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1

et al. 2012

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Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), initially named anamorsin, a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway. Current study has revealed that CIAPIN1 may have wide and important functions, especially due to its close correlations with malignant tumors. However whether or not it is involved in the multi-drug resistance (MDR) process of breast cancer has not been elucidated. To explore the effect of CIAPIN1 on MDR, we examined the expression of P-gp and CIAPIN1 by immunohistochemistry and found there was positive correlation between them. Then we successfully interfered with RNA translation by the infection of siRNA of CIAPIN1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced significantly and the expression of MDR1mRNA and P-gp in MCF7/ADM cell lines showed a significant decrease. Also the expression of P53 protein increased in a statistically significant way (p ≤ 0.01) after RNAi exposure. In addition, flow cytometry analysis reveals that cell cycle and anti-apoptotic enhancing capability of cells changed after RNAi treatment. These results suggested CIAPIN1 may participate in breast cancer MDR by regulating MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic capability of cells.

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Section: Resultsmentioning

confidence: 99%

Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1

et al. 2012

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“…The natural red fluorescence of the chemotherapeutic drug ADM was used to determine drug accumulation and retention[ 36 ]. Briefly, HepG2 cells transfected with pEGFP-ZHX2 were cultured in medium with 40μg/ml ADM for 4 hours at 37 o C. Drug accumulation in the cells was estimated either by fluorescence microscope or flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA

Yue

Gao

et al. 2014

Oncotarget

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We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated suppression of liver tumor growth in vivo. Furthermore, immunohistochemical staining demonstrated the inverse correlation of ZHX2 and MDR1 expression in HCC tissues. Luciferase report assay showed that ZHX2 repressed the MDR1 promoter activity, while knockdown of NF-YA or mutating the NF-Y binding site eliminated this ZHX2-mediated repression of MDR1 transcription. Co-IP and ChIP assay further suggested that ZHX2 interacted with NF-YA and reduced NF-Y binding to the MDR1 promoter. Taken together, we clarify that ZHX2 represses NF-Y-mediated activation of MDR1 transcription and, in doing so, enhances the effects of chemotherapeutics in HCC cells both in vitro and in vivo.

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“…The current study showed that P-gp expression was suppressed while wild-type P53 expression was upregulated when CIAPIN1 expression was downregulated. Since MCF-7 cells harbor wild-type P53 (26), we assumed that the CIAPIN1 gene may upregulate P-gp expression by regulating wild-type P53 expression, leading to breast cancer resistance. However, there are controversies about the modulation of P-gp expression by P53 in the different cancer cell lines that have been studied (23-26).…”

Section: Discussionmentioning

confidence: 99%

“…Since MCF-7 cells harbor wild-type P53 (26), we assumed that the CIAPIN1 gene may upregulate P-gp expression by regulating wild-type P53 expression, leading to breast cancer resistance. However, there are controversies about the modulation of P-gp expression by P53 in the different cancer cell lines that have been studied (23-26). It must be emphasized that this study was performed using only MCF-7/ADM cells, and whether this conclusion still holds for other breast cancer cell lines still needs further study.…”

Section: Discussionmentioning

confidence: 99%

CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

Wang

Gao

Guo

et al. 2014

Braz J Med Biol Res

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Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

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CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53

Cited by 7 publications

References 14 publications

Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1

Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1

ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA

CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

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