Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

Yu, Zhen; Zhang, Chang; Wang, Hao; Xing, Junjie; Gong, Haifeng; Yu, Enda; Zhang, Wei; Zhang, Xiaoqing; Cao, Guangwen; Fu, Chuangang

doi:10.1016/j.canlet.2014.07.025

Cited by 30 publications

(31 citation statements)

References 41 publications

(39 reference statements)

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“…Besides, CXCR4 silencing increased the expression of p-caspase-3 and Bax, which were proved to be essential regulators of apoptosis process. 24,25 In conclusion, our study demonstrates that CXCR4 is overexpressed in TSCC CDDP cells. CXCR4 silencing significantly suppressed cell proliferation, induced apoptosis and enhanced its sensitivity to cisplatin.…”

Section: Increasing Evidences Show That Patients With Higher Cxcr4mentioning

confidence: 53%

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CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Zhuang

Zhou

2018

J Oral Pathology Medicine

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Background The chemokine receptor 4 (CXCR4) plays an important role in tumor progression. Overexpressed CXCR4 is associated with a poor prognosis of patient with head and neck squamous cell carcinomas. However, the correlation between CXCR4 and chemotherapy resistance in tongue squamous cell carcinoma (TSCC) remains obscure. Methods Stable cisplatin‐resistant CAL27 CDDP and SCC25 CDDP cells were established and identified by CCK8 assay, and the CXCR4 expression was detected using qRT‐PCR and Western blot. CXCR4‐siRNA was transfected into TSCC CDDP cells, whose transfect efficiency was examined. Cisplatin sensitivity was further detected, as well as several proliferation and apoptosis‐related proteins. Results CAL27 CDDP and SCC25 CDDP cells were successfully established, which exhibited significantly higher cell viability and less apoptosis under cisplatin stimulation than that of parental cells. CXCR4 expression was increased in TSCC CDDP cells. After transfection of CXCR4‐siRNA, the expression of CXCR4 was reduced by 73% and 78% in CAL27 CDDP and SCC25 CDDP cells, respectively. CCK8 assay and flow cytometry assay revealed that the proliferative capacity under cisplatin stimulation significantly decreased after CXCR4 silencing. Moreover, increased TSCC CDDP cells were arrested in the G0/G1 phase after knockdown of CXCR4. Compared with negative control group, the expression of cyclin D1 and p‐AKT decreased, while that of p‐caspase‐3 and Bax significantly increased. Conclusions Silencing CXCR4 may evidently inhibit proliferation, induce apoptosis and enhance cisplatin sensitivity of TSCC CDDP cells by reduced cyclin D1 and p‐AKT, and increased p‐caspase‐3 and Bax.

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Section: Increasing Evidences Show That Patients With Higher Cxcr4mentioning

confidence: 53%

“…Our results showed that the both cyclin D1 and p‐AKT expression were significantly reduced in TSCC CDDP cells with CXCR4 silencing. Besides, CXCR4 silencing increased the expression of p‐caspase‐3 and Bax, which were proved to be essential regulators of apoptosis process …”

Section: Discussionmentioning

confidence: 99%

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Zhuang

Zhou

2018

J Oral Pathology Medicine

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“…51 Finally, the negative effect on pathological response of aberrant expression of MRP3, another member of this family, was recently shown by Yu et al in 144 pretreatment rectal biopsies from patients treated with NCRT. 52 With regard to protein microarray technologies, Mammano et al published an interesting report in 2012 based on a new method for quantitative multiplexed analysis of protein signaling activation. Although the case series was very small (n ¼ 15) and submitted to heterogeneous chemotherapy, the authors evaluated a wellcontrolled clinical study set of tumor biopsies, and concluded that an activated state of the phosphatidylinositol 3-kinase-v-akt murine thymoma viral oncogene homolog pathway could be used to stratify patients.…”

Section: Protein Expressionmentioning

confidence: 99%

Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

Molinari

Matteucci

Caroli

et al. 2015

Clinical Colorectal Cancer

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“…Both etoposide and teniposide have been shown to be substrates of ABCC3, although these drugs are not in clinical use for chemotherapy in patients with CRC. The sensitivity of the colon cancer cell lines HT‐29 and SW480 to 5‐FU, which is the most widely used drug in the treatment of CRC, was found to be increased by RNAi‐mediated depletion of ABCC3 . Moreover, a previous microarray analysis showed that the abundance of ABCC3 mRNA was increased in 5‐FU‐resistant HCT 116 cells (Fig.…”

Section: Discussionmentioning

confidence: 85%

Wnt‐β‐catenin signaling regulates ABCC3 (MRP3) transporter expression in colorectal cancer

et al. 2016

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We determined the gene expression profiles for 48 ATP binding cassette (ABC) transporters in matched colon cancer and normal colon tissues in order to provide insight into the mechanisms underlying expression of transporters related to colon carcinogenesis. The expression of ABCB1,ABCC1,ABCC2,ABCC3, and ABCG2 was altered in association with colon carcinogenesis. Among these transporters, the expression of ABCC3 was repressed by Wnt signaling pathway in colon cancer cell lines. Knockdown of the pathway components transcription factor 7‐like 2 (TCF7L2) or β‐catenin thus increased ABCC3 expression, whereas activation of Wnt signaling with inhibitors of glycogen synthase kinase–3β (GSK‐3β) reduced it. ChIP and luciferase reporter assays also showed that TCF7L2 binds to the ABCC3 locus and regulates its expression. Finally, overexpression of ABCC3 in colon cancer cells conferred resistance to anticancer drug‐induced cytotoxicity. Our data thus suggest that Wnt signaling represses ABCC3 expression during colon carcinogenesis, and that subsequent upregulation of ABCC3 expression during drug treatment might contribute to acquired drug resistance.

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Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

Cited by 30 publications

References 41 publications

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

Wnt‐β‐catenin signaling regulates ABCC3 (MRP3) transporter expression in colorectal cancer

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