Synergistic induction of apoptosis by salinomycin and gefitinib through lysosomal and mitochondrial dependent pathway overcomes gefitinib resistance in colorectal cancer

Zou, Zhengzhi; Nie, Peipei; Li, Yawei; Hou, Benxin; Rui-li,; Shi, X.; Ma, Zhaokui; Han, Baowei; Xin-xing, Luo

doi:10.18632/oncotarget.5628

Cited by 43 publications

(24 citation statements)

References 43 publications

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“…For luciferase assay, the 293T and A549 cells were cultured in 24-well plates and transfected with 500 ng of either pGL3-FOXM1 or pGL3-control vector and 50 pmol of miR-509- [25].…”

Section: Dual-luciferase Activity Assaymentioning

confidence: 99%

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer

Zhang

Qiao

et al. 2016

Cell Physiol Biochem

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Background/Aims: Deregulation of microRNAs (miRNAs) expression is a frequent event in cancer development and progression. Recent studies have implied that abnormal expression of miRNAs is frequently observed in non-small cell lung cancer (NSCLC). Here, we examined the levels and biological functions of miR-509-5p in NSCLC. Methods: The levels of miR-509-5p were measured by real-time quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with adjacent normal tissues. Cell viability was analyzed by MTT and colony formation assay. Cell migration and invasion were evaluated by transwell and wound healing assay. In addition, we predicted the putative targets of miR-509-5p by bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the relationship between miR-509-5p and the target in NSCLC cells. Results: miR-509-5p expression was significantly reduced in NSCLC tissues compared with adjacent normal tissues. In addition, miR-509-5p decreased cell proliferation, migration and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase reporter assay showed miR-509-5p could bind to the 3' untranslational regions of FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability, migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299 cells. Conclusions: miR-509-5p exerts tumor-suppressive effects by attenuating FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR-509-5p may be considered as a novel and potential target for the diagnosis, prognosis and treatment of NSCLC.

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“…For luciferase assay, the 293T and A549 cells were cultured in 24-well plates and transfected with 500 ng of either pGL3-FOXM1 or pGL3-control vector and 50 pmol of miR-509- [25].…”

Section: Dual-luciferase Activity Assaymentioning

confidence: 99%

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer

Zhang

Qiao

et al. 2016

Cell Physiol Biochem

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“…Salinomycin was also utilized as additive in several other combinational treatment approaches overcoming acquired drug resistance [20, 21]. …”

Section: Introductionmentioning

confidence: 99%

Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases

et al. 2016

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Luminal A breast cancer is the most common breast cancer subtype which is usually treated with selective estrogen receptor modulators (SERMS) like tamoxifen. Nevertheless, one third of estrogen receptor positive breast cancer patients initially do not respond to endocrine therapy and about 40% of luminal A breast tumors recur in five years. In this study, we investigated an alternative treatment approach by combining tamoxifen and salinomycin in luminal A breast cancer cell lines. We have found that salinomycin induces an additional cytotoxic effect by inhibiting the ligand independent activation of ERα. Thereby salinomycin increases the intracellular calcium level. This leads to a premature fusion of endosomes with lysosomes and thus to the degradation of Egfr family members. Since this process is essential for luminal A breast cancer cells to circumvent tamoxifen treatment, the combination of both drugs induces cytotoxicity in tamoxifen sensitive as well as resistant luminal A breast cancer cell lines.

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“…Chemotherapy is an important treatment strategy for solid tumors, and one of the main treatment methods for CRC (17,18). Apoptosis is one of the main signs of effective anticancer chemotherapy; however, due to drug resistance, the apoptotic effects of drugs on the tumor cells are weakened and a large proportion of patients respond poorly to chemotherapy (19,20). At present, drug resistance of tumor cells is one of the main reasons for chemotherapy failure (21).…”

Section: Mirnas and Chemotherapy For Crcmentioning

confidence: 99%

“…By contrast, inhibition of miRNA-587 may enhance the expression of PPP2R1B in CRC cells, which increases sensitivity to 5-FU treatment. Previous studies indicated that miRNA-302a expression is decreased in CRC cells, and high expression of miRNA-302a inhibits cell proliferation through inactivating ERK1/2 and PI3K/AKT (17,20). Oxaliplatin (L-OHP) is a third-generation platinum-based chemotherapy agent.…”

Section: Mirnas and Chemotherapy For Crcmentioning

confidence: 99%

Role of microRNAs in the resistance of colorectalï¿½cancer to chemoradiotherapy (Review)

Sheng

Zhang

et al. 2018

mol clin onc

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Abstract. Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1. The miR-34a mimic MRX34 is the first synthetic miRNA to have been entered into clinical trials. miR-21 prevents tumor cell stemness, invasion and drug resistance, which are required for the development of CRC. These findings suggest that miRNAs represent a focus in the research of novel cancer treatments aimed at sensitizing cancer cells to chemotherapeutic drugs. The aim of the present study was to review the functions of miRNAs and investigate the roles of miRNAs in CRC radioresistance or chemoresistance. Furthermore, the potential of including miRNAs in therapeutic strategies and using them as molecular biomarkers for predicting radiosensitivity and chemosensitivity was discussed.

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Synergistic induction of apoptosis by salinomycin and gefitinib through lysosomal and mitochondrial dependent pathway overcomes gefitinib resistance in colorectal cancer

Cited by 43 publications

References 43 publications

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer

Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases

Role of microRNAs in the resistance of colorectalï¿½cancer to chemoradiotherapy (Review)

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