Inhibition of IGF‐IR increases chemosensitivity in human colorectal cancer cells through MRP‐2 promoter suppression

Shen, Ke; Cui, Daling; Sun, Liankun; Lü, Yanhua; Han, Mingquan; Liu, Jianwen

doi:10.1002/jcb.24080

Cited by 35 publications

(20 citation statements)

References 35 publications

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“…P-glycoprotein (P-gp) is a plasma membrane glycoprotein often involved in the resistance of cancer cells towards multiple anticancer agents (19). To further confirm the 5-FU-resistant phenotype, mrna expression of P-gp in SW620/5-fu cells was examined by quantitative rt-Pcr.…”

Section: Resultsmentioning

confidence: 99%

Knockdown of β3GnT8 reverses 5-fluorouracil resistance in human colorectal cancer cells via inhibition the biosynthesis of polylactosamine-type N-glycans

Shen

et al. 2014

International Journal of Oncology

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Abstract. aber rant glycosylation is known to be associated with cancer chemoresistance. β-1,3-n-acetylglucosaminyltransferase (β3gnt)8, which synthesizes polylactosamine on β1-6 branched n-glycans, is dramatically upregulated in colorectal cancer (crc). 5-fluorouracil (5-fu) resistance remains a major obstacle to the chemotherapy of crc. However, little is known with regard to the correlation between 5-fu resistance and the expression of β3gnt8 in crc. in this study, a 5-fu-resistant cell line (SW620/5-fu) was generated, and 50% inhibition concentration (ic50) of 5-fu was determined by Mtt assay. flow cytometry and lectin blot analysis were performed to detect the alteration of polylactosamine structures. Quantitative rt-Pcr and western blot analysis were used to identify and evaluate candidate genes involved in the synthesis of polylactosamine in SW620/5-fu cells. We found polylactosamine chains were significantly increased in SW620/5-fu cells. inhibition of the biosynthesis of polylactosamine by 3'-azidothymidine (aZt) was able to reduce 5-fu tolerance. further studies showed that β3gnt8 expression was also upregulated in 5-fu-resistant cancer cells, and knockdown of β3gnt8 by rna interference reversed 5-fu resistance through, at least partly, by suppressing the formation of polylactosamine. in conclusion, the alteration of β3gnt8 in crc cells correlates with tumor sensitivity to the chemotherapeutic drug and has significant implication for the development of new treatment strategies.

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Section: Resultsmentioning

confidence: 99%

Knockdown of β3GnT8 reverses 5-fluorouracil resistance in human colorectal cancer cells via inhibition the biosynthesis of polylactosamine-type N-glycans

Shen

et al. 2014

International Journal of Oncology

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“…Insulin-like growth factor receptor (IGF-IR) is an upstream regulatory molecule of Akt and ERK. A recent study reported that IGF-IR was highly expressed in MDR colorectal cells, and that silencing IGF-IR decreased proliferation of MDR cells [16]. Additionally, after IGF-1 stimulation, c-Cbl associated with IGF-IR and mediated receptor polyubiquitination [17].…”

mentioning

confidence: 97%

The E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells

Che¹,

Zhang²,

Qu³

et al. 2017

neo

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Most receptor tyrosine kinases (RTKs) contribute to tumor growth, and their ubiquitination and degradation is related to the inhibition of tumor growth. Our previous study showed that the ubiquitin ligase Cbl-b was expressed at low levels in multidrug-resistant (MDR) gastric cancer cells compared with their parental cells. However, whether enhancement of Cbl-b expression in MDR cancer cells could prevent tumor proliferation via ubiquitination and degradation of RTK remains unclear. In the present study, Cbl-b overexpression reduced cell proliferation in MDR gastric and breast cancer cells, and effectively inhibited tumor growth in vivo. Additionally, Cbl-b overexpression reduced the total protein level of insulin-like growth factor 1 (IGF-1R), an important member of the RTK family. Moreover, Cbl-b overexpression promoted interaction of Cbl-b with IGF-1R, and induced ubiquitination and degradation of IGF-1R and inactivation of the IGF-1R pathway. These results suggest that the ubiquitin ligase Cbl-b inhibited tumor growth via ubiquitination and degradation of IGF-1R in MDR gastric and breast cancer cells.

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“…IGF1R signals participate in regulating ABC genes, including multidrug resistance protein 1 (MDR1), MRP1, multidrug resistance-associated protein 2 (MRP2), multidrug resistance-associated protein 3 (MRP3) and breast cancer resistance protein (BCRP) (59,87-89). As such, IGF1R increases tumor resistance by increasing the expression of MDR1, a protein implicated in chemotherapeutic resistance (88). Expression of MRP3 and BCRP decreases or disappears in the presence of an IGF1R inhibitor (87) and overexpressing IGF1R results in increased MRP2 promoter activity via increased pAKT and nuclear factor erythroid 2-related factor 2 in resistant cells (59,88).…”

Section: Igf1r and Chemotherapy Resistancementioning

confidence: 99%

“…In addition, IGF1R silencing increases chemotherapeutic sensitivity via transcription inhibition of MRP-2 (59). Previous studies have demonstrated that overexpressing IGF1R and MRP1 was associated with chemotherapeutic resistance and poorer prognosis compared with malignancies with normal or low expression of IGF1R and MRP1, indicating that the co-expression of IGF1R/MRP1 in tumors may predict chemotherapeutic effects (88,89).…”

Section: Igf1r and Chemotherapy Resistancementioning

confidence: 99%

Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

et al. 2017

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Abstract. Drug resistance is a primary cause of chemotherapeutic failure; however, how this resistance develops is complex. A comprehensive understanding of chemotherapeutic resistance mechanisms may aid in identifying more effective drugs and improve the survival rates of patients with cancer. Insulin-like growth factor 1 receptor (IGF1R), a member of the insulin receptor family, has been extensively assessed for biological activity, and its putative contribution to tumor cell development and progression. Furthermore, researchers have attended to drugs that target IGF1R since IGF1R functions as a membrane receptor. However, how IGF1R participates in chemotherapeutic resistance remains unclear. Therefore, the present study described the IGF1R gene and its associated signaling pathways, and offered details of IGF1R-induced tumor chemoresistance associated with promoting cell proliferation, inhibition of apoptosis, regulation of ATP-binding cassette transporter proteins and interactions with the extracellular matrix. The present study offered additional explanations for tumor chemotherapy resistance and provided a theoretical basis of IGF1R and its downstream pathways for future possible chemotherapy treatment options.

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Inhibition of IGF‐IR increases chemosensitivity in human colorectal cancer cells through MRP‐2 promoter suppression

Cited by 35 publications

References 35 publications

Knockdown of β3GnT8 reverses 5-fluorouracil resistance in human colorectal cancer cells via inhibition the biosynthesis of polylactosamine-type N-glycans

Knockdown of β3GnT8 reverses 5-fluorouracil resistance in human colorectal cancer cells via inhibition the biosynthesis of polylactosamine-type N-glycans

The E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells

Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

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