Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

Fang, Xin Jian; Jiang, Hua; Zhu, Ya Qun; Zhang, Liyuan; Fan, Qiu Hong; Tian, Ye

doi:10.3892/or.2014.3131

Cited by 72 publications

(37 citation statements)

References 23 publications

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“…At present, the precise mechanism by which doxorubicin upregulates DR transcripts is not clear but it may involve activation of NF-κB pathway. As a shared transcription factor for all four DRs, NF-κB was shown to be activated in multiple cancer types in response to doxorubicin treatment155152. Nonetheless, the ability of doxorubicin to upregulate DRs in cardiomyocytes provides critical insight into the molecular mechanisms of the adverse drug reaction.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes

Zhao

Zhang

2017

Sci Rep

292

185

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Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Here we investigated doxorubicin-induced cytotoxicity in human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs). We found that doxorubicin and related anthracycline agents (e.g., daunorubicin, idarubicin, and epirubicin) significantly upregulated the expression of death receptors (DRs) (TNFR1, Fas, DR4 and DR5) in iPS-derived cardiomyocytes at both protein and mRNA levels. The resulting iPS-CMs cells underwent spontaneous apoptosis which was further enhanced by physiologically relevant death ligands including TNF-related apoptosis inducing ligand (TRAIL). Furthermore, TRAIL potentiated doxorubicin-induced decrease in beating rate and amplitude of iPS-derived cardiomyocytes. These data demonstrate that the induction of death receptors in cardiomyocytes is likely a critical mechanism by which doxorubicin causes cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes

Zhao

Zhang

2017

Sci Rep

292

185

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“…However, the DNA damage induced by doxorubicin activates the NF-κB pathway, leading to doxorubicin resistance in cancer cell lines, including in breast cancer cells15161718.…”

mentioning

confidence: 99%

The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment

Kim

Jung

Ahn

et al. 2016

Sci Rep

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We investigated gene expression profiles of the NF-κB pathway in patients with triple-negative breast cancer (TNBC) receiving adjuvant chemotherapy to determine the prognostic value of NF-κB pathway genes according to chemotherapeutic regimen. We used the nCounter expression assay to measure expression of 11 genes (NFKB1, NFKB2, RELA, RELB, REL, TP53, FOXC1, TBP, SP1, STAT3 and IRF1 genes) belonging to the NF-κB pathway using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Of the 203 patients, 116 were treated with a chemotherapeutic regimen containing doxorubicin. As revealed by the expression profiles of the 11 genes, increased expression of SP1 was associated with poor prognosis in TNBC patients treated with adjuvant doxorubicin chemotherapy (5-year distant recurrence-free survival [5Y DRFS], low vs. high expression [cut-off: median]: 92.3% vs. 71.6%, P = 0.001). In a multivariate Cox regression model, SP1 expression was a useful marker for predicting long-term prognosis in TNBC patients receiving doxorubicin treatment, and we thus suggest that SP1 expression could serve as a prognostic marker in these patients.

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“…Those studies showed that hyaluronan upregulates the expression of MMP2 and MMP9 by interacting with CD44st, and thus increases the aggressiveness of MCF-7 cells. The CD44st gene is probably also associated with aggressiveness, metastasis, and prognosis of breast cancer [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Expression of Novel CD44st and MMP2 in NSCLC Tissues and Their Clinical Significance

Zhang

Hai

et al. 2017

Oncol Res Treat

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Background: Abnormal expression of some CD44 molecules in tumor tissues can induce the degradation of the extracellular matrix, and is closely associated with axillary lymph node metastasis, angiogenesis, cancer progression, and drug resistance. Patients and Methods: We measured and confirmed the expression of CD44st and MMP2 mRNAs and proteins in the cancer tissues and adjacent normal tissues of postoperative non-small cell lung cancer (NSCLC) patients with either adenocarcinoma (n = 72) or squamous cell carcinoma (n = 53) using quantitative reverse transcription polymerase chain reaction, gene sequencing, and immunohistochemical analysis. Results: CD44st and MMP2 expression were closely associated with the histopathological classification, lymph node metastasis, and TNM stage of the tumors, and the difference was statistically significant (p < 0.05). The median overall survival (OS) for the high CD44st expression group was 30.52 months (95% confidence interval (CI) 24.02-36.15); for the low expression group it was 43.23 months (95% CI 31.81-52.02) (p = 0.020). The median OS for the high MMP-2 expression group was 30.53 months (95% CI 26.69-33.31); for the low expression group it was 40.06 months (95% CI 33.55-46.45) (p = 0.022). Conclusion: The rates of CD44st and MMP2 expression were higher in squamous cell carcinomas than in adenocarcinomas, were closely associated with lymph node metastasis and TNM stage, and affected patients' prognoses.

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Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

Cited by 72 publications

References 23 publications

Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes

Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes

The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment

Expression of Novel CD44st and MMP2 in NSCLC Tissues and Their Clinical Significance

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